Method for treating a neurological disorder

ABSTRACT

A therapeutic method for treating a neurological disease by accessing a neuraxial deformity and abnormal neuraxial stress. The method involves calculating a neuraxial stress, determining whether the neurological disorder is attributed at least in part to the neuraxial stress; and treating the neurological disorder by normalizing the neuraxial stress.

This application is: (1) a continuation in part of U.S. patentapplication Ser. No. 12/638,930, filed Dec. 15, 2009; which in turn, isa continuation in part of U.S. patent application Ser. No. 12/350,936,filed Jan. 8, 2009; which, in turn, claims benefit of priority to U.S.Provisional Patent Application No. 61/019,622, filed Jan. 8, 2008, U.S.Provisional Patent Application No. 61/098,456, filed Sep. 19, 2008, U.S.Provisional Patent Application No. 61/104,862, filed Oct. 13, 2008, U.S.Provisional Patent Application No. 61/122,506, filed Dec. 15, 2008, andU.S. Provisional Patent Application No. 61/138,031, filed Dec. 16, 2008;and (2) a continuation in part of U.S. patent application Ser. No.12/688,848, filed Jan. 15, 2010; which in turn, is a continuation inpart of U.S. patent application Ser. No. 12/350,936, filed Jan. 8, 2009;which, in turn, claims benefit of priority to U.S. Provisional PatentApplication No. 61/019,622, filed Jan. 8, 2008, U.S. Provisional PatentApplication No. 61/098,456, filed Sep. 19, 2008, U.S. Provisional PatentApplication No. 61/104,862, filed Oct. 13, 2008, U.S. Provisional PatentApplication No. 61/122,506, filed Dec. 15, 2008 and U.S. ProvisionalPatent Application No. 61/138,031, filed Dec. 16, 2008; U.S. patentapplication Ser. No. 12/688,848 is also a continuation in part of U.S.patent application Ser. No. 11/832,643, filed on Aug. 1, 2007, which inturn claims the benefit of U.S. Provisional Patent Application No.60/887,022, filed on Jan. 29, 2007; U.S. patent application Ser. No.12/688,848 is further a continuation in part of U.S. patent applicationSer. No. 11/832,646, filed on Aug. 1, 2007, which in turn claims thebenefit of U.S. Provisional Patent Application No. 60/887,022, filed onJan. 29, 2007; the entire disclosures of which are incorporated hereinby reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a method and system for spinalfixation, stabilization and/or fusion of the human occipito-cervicaljunction. Additionally, the invention is further directed to a methodand apparatus for the treatment of an abnormal neuraxial angle, abnormalclivo-axial angle and mitigation of neurological conditions underlyingneurobehavioral disorders arising as a result of abnormalities of theneuraxial angle, clivo-axial angle, skull base, craniocervical,posterior fossa and combinations thereof, which, without wishing to bebound by theory in a subset of individuals, cause neuro-behavioraldisorders such as autism, autism spectrum of disorders, bipolar disorderand other neurological disorders. The present invention is directed tothe treatment of these neurological disorders through the recognition,diagnosis, normalization of the craniospinal relationship by fixation,stabilization and/or fusion of the human occipito-cervical junction.

2. Description of the Related Technology

The normal range of motion of the craniospinal junction includes about27° of flexion and extension, and 90° of lateral rotation; thecraniospinal junction is thus the most mobile and articulatable part ofthe human body. It is also the most active part of the human body inmovement throughout the day, typically performing greater than 3 millionmotions a year. The craniospinal junction transmits the entire nervousstructure to the body (with the exception of the vague nerve), and isthus unfortunately susceptible to a host of degenerative disorders.Other common causes of cranio-cervical instability, include traumaticfractures, which can account for approximately 3,000 fractures of theupper spine related to head trauma each year; congenital diseases, suchas Ehlers Danlos syndrome, Down's syndrome, Morquio's syndrome andspondyloepiphysial dysplasia syndrome, with a prevalence of at least50,000; and osteogenesis imperfecta, with a prevalence of 7,000patients. There are numerous causes of bone softening related tomalabsorption syndromes and other renal/metabolic and endocrinesyndromes that result in abnormal craniospinal relationships.Additionally, cancer and infections that involve the craniocervicaljunction. can cause destruction of the stabilizing elements.

Among the patients suffering from craniocervical abnormalities, aresubsets of individuals diagnosed with neurological disorders, such assleep apnea, dyslexia, GERDS, speech dyspraxia, idiopathic scoliosis,and neuropsychiatric disorders, such as autism spectrum of disorders(eg. Asperger's Syndrome), Attention Deficit Hyperactivity Disorder,scizophrenia, bipolar disease, depression and anxiety disorders. Theneurological and neurosurgical literature has reported instances whereneurological symptoms appear to have been associated with retroflexionof the odontoid, platybasia and select forms of basilar invagination.The clivioaxial angle is depicted in FIG. 1, while an example of basilarinvagination causing visible compression of the brainstem is shown inFIG. 2, which has been associated with sleep apnea, delayed speech,gastroesophageal reflux, and altered behavior, such as attention deficitdisorder, headaches, and a myriad of other sensori-motor syndromes.Additionally, the presence of a Chiari malformation has been associatedwith scoliosis, GERDS, sleep apnea and unusual neurological findingssuch as trigemenial neuralgia, and tongue thrusting. The prior art,however, has yet to recognize a relationship between deformative stressof the brainstem and neurobehavioral disorders or contemplate treatmentof a neurological disorder by reducing or eliminating the deformativestress.

A need exists for a system and methodology that accomplishes the goalsof recognition of the subtler forms of craniocervical and correspondingmedullospinal deformity as a cause of neurological disorders andconditions, measurement of the deformity, and the reduction orcorrection of deformity through normalization of the craniospinalrelationship to effectively treat the neurological disorders.

SUMMARY OF THE INVENTION

The invention is directed to a method for treating a neurologicaldisorder. In a first aspect, the method involves: calculating aneuraxial stress of an individual; determining whether the neurologicaldisorder is attributed at least in part to the calculated neuraxialstress; and treating the neurological disorder by normalizing theneuraxial stress.

In a second aspect, the method is directed to a treatment for aneurological behavioral disorder that involves: determining whether aneuraxial deformity an individual diagnosed with a neurologicalbehavioral disorder is substantially contributing to or causes theneurological behavioral disorder; and treating the neurologicalbehavioral disorder by normalizing the clivo-axial angle.

In a third aspect, the method is directed to a treatment forcranio-vertebral instability. The method involves: treating anindividual having an existing cranio-vertebral instability by accessingthe presence of an abnormal neuraxial angle and/or abnormal clivo-axialangle in the individual; and normalizing the clivo-axial angle or theneuraxial angle.

In a fourth aspect, the method is directed to a treatment for aneurological disorder resulting from cranio-vertebral instability. Themethod involves accessing the presence of an abnormal neuraxial angleand/or abnormal clivo-axial angle in the individual, wherein theindividual has an existing cranio-vertebral instability; and treatingthe neurological disorder resulting from cranio-vertebral instability bynormalizing a clivo-axial angle or a neuraxial angle of the individual.

These and various other advantages and features of novelty thatcharacterize the invention are pointed out with particularity in theclaims annexed hereto and forming a part hereof. However, for a betterunderstanding of the invention, its advantages, and the objects obtainedby its use, reference should be made to the drawings which form afurther part hereof, and to the accompanying descriptive matter, inwhich there is illustrated and described a preferred embodiment of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a fragmentary perspective view of a system for effectingfusion of the human occipitocervical junction according to an exemplaryembodiment of the invention;

FIG. 2 is a fragmentary cross-sectional view of a portion of the systemthat is depicted in FIG. 1;

FIG. 3 is a fragmentary perspective of an exemplary embodiment of adrill guide positioned on the occiput of the cranium for creatingoblique screw holes;

FIG. 4 is a fragmentary perspective of a triple threaded screw obliquelyinserted in the occiput;

FIG. 5 is a fragmentary cross-section showing a drill bit received inthe drill guide and creating an oblique screw hole in the occiput bone;

FIG. 6 is a fragmentary perspective of a drill angularly received indrill guide;

FIG. 7( a) is a fragmentary perspective view of a system for effectingfusion of the human occipitocervical junction using an articulating rodsystem;

FIG. 7( b) is a fragmentary perspective view of a system for effectingfusion of the human occipitocervical junction using an alternativearticulating rod system;

FIG. 8( a) is a fragmentary cross-sectional view depicting a fasteningassembly that is constructed according to a preferred embodiment of theinvention;

FIG. 8( b) is a fragmentary top plan view of the fastening assembly thatis depicted in FIG. 8( a);

FIG. 9( a) is a fragmentary cross-sectional view depicting anotherfastening assembly that is constructed according to a preferredembodiment of the invention;

FIG. 9( b) is a fragmentary top plan view of the fastening assembly thatis depicted in FIG. 9( a);

FIG. 10 is a diagrammatical depiction of a fastening tool that isdesigned to be used in conjunction with the fastening assembly that isdepicted in FIGS. 8( a)-9(b), shown in a first operative position;

FIG. 11 is a diagrammatical depiction of the fastening tool that isshown in FIG. 10, shown in a second operative position;

FIG. 12 is a fragmentary side elevational view of one component of thesystem that is depicted in FIG. 1;

FIG. 13 is a fragmentary perspective view showing another embodiment ofthe invention;

FIG. 14 is a cross-sectional view depicting certain components of thesystem that is shown in FIG. 1;

FIG. 15 is a fragmentary cross-sectional view depicting certaincomponents of the portion of the system shown FIG. 1 that is depicted inFIG. 14;

FIG. 16 is a diagrammatical depiction of certain components of theportion of the system that is shown in FIG. 14;

FIG. 17 is a perspective view of an exemplary embodiment of a C1attachment system being utilized to connect the C1 vertebra to anothersystem that stabilizes the skull and spine;

FIG. 18( a) is a perspective view of an exemplary embodiment of theclamp;

FIG. 18( b) is a perspective view of an exemplary embodiment of theclamp on the posterior region arch of the C1 vertebra;

FIG. 18( c) shows a drill creating a hole that penetrates the posteriorarch of the C1 vertebra from the dorsal to ventral side;

FIG. 18( d) is a perspective view of a screw placed through the clampand adjacent to the posterior arch of the C1 vertebra;

FIG. 19 is a cross section of a screw placed through the plate, theclamp, and posterior arch of the C1 vertebra that is secured with aspiral locking mechanism in the screw head;

FIG. 20 is a perspective view of an exemplary attachment system wrappingaround the spinous process of the thoracic vertebra using subliminalscrews;

FIG. 21( a) is a top view of an exemplary embodiment of a plate;

FIG. 21( b) is a side view of an exemplary embodiment of the plate shownin FIG. 21( a);

FIG. 22( a) is a perspective view of an attachment system wherein theclamps and plate are constructed as an integral device;

FIG. 22( b) is a perspective view of the attachment system of FIG. 21(a) fastened to an occiput plate;

FIG. 22( c) is a perspective view of the attachment system of FIG. 21(a) with an applied bone graft material;

FIG. 23( a) shows a perspective view of an exemplary cranial attachmentsystem positioned along a perimeter of a calvarial defect;

FIG. 23( b) shows a perspective view of the cranial attachment system ofFIG. 22( a) enclosing an edge of the calvarial defect;

FIG. 23( c) shows an exemplary cranial clamp including a base member anda plurality of extension members;

FIG. 24( a) shows an exemplary embodiment of a connector;

FIG. 24( b) shows another exemplary embodiment of a connector;

FIG. 24( c) shows a third exemplary embodiment of a connector;

FIG. 25( a) shows a guide plate in conjunction with a connector;

FIG. 25( b) shows another view of the guide plate in conjunction with aconnector;

FIG. 26 shows a dorsal inferior view of the transvertebral stabilizationsystem including a connector, two connector assemblies and a systemfastener;

FIG. 27 shows an exemplary embodiment of a connector with a sprocketdrive;

FIG. 28 shows an exemplary embodiment of a connector that does notpenetrate the spinous process;

FIG. 29( a) shows an exemplary embodiment of the post of the connectorassembly;

FIG. 29( b) shows an exemplary embodiment of the cap of the connectorassembly;

FIG. 30( a) shows an exemplary embodiment of the osteointegrationapparatus oriented on the subocciput, C1 vertebra and C2 vertebra;

FIG. 30( b) is a cross-section of an exemplary embodiment of theosteointegration apparatus showing the device attached from the skull toC2;

FIG. 31( a) shows another exemplary embodiment of the osteointegrationapparatus oriented on the subocciput, C1 vertebra and C2 vertebra with abone graft material oriented on the midline fold of device;

FIG. 31( b) is a cross-section of an exemplary modular embodiment of theosteointegration apparatus with a plurality of independently movablesegments;

FIG. 32 is a cross-section an exemplary embodiment of theosteointegration apparatus attached through C2 spinous process and C2lateral mass;

FIG. 33( a) is a fragmentary perspective of the C1 vertebral attachmentsystem showing a fastener penetrating a trabecular mesh porous body andthe C1 posterior arch;

FIG. 33( b) is a fragmentary perspective of the C1 vertebral attachmentsystem engaging the osteointegration apparatus;

FIG. 34 shows an apparatus for testing trial clamps;

FIG. 35 shows a connector being guided with forceps;

FIG. 36 shows an anatomical cross-sectional image of a brainstem;

FIG. 37 is a calculation demonstrating that strain may be expressed asthe thickness of the neuraxis divided by the length of the radius of thearc subtended by the angle σ ver the deformity;

FIG. 38 is a graph of conduction amplitude as a function of strain.

FIG. 39( a) shows a normal craniocervical junction in the neutralposition, wherein the cllivoaxial angle as depicted is about 150° andthere is minimal neuraxial strain.

FIG. 39( b) shows a normal craniocervical junction in flexion, whereinthe neuraxis stretches approximately 10% of its total length withflexion of the cervical junction creating a strain of about 0.1.

FIG. 39( c) shows a pathological craniocervical junction with anabnormal clivo-axial angle in the neutral position as a result ofmedullary kyphosis, wherein the restraining strain is about 0.1.

FIG. 39( d) shows a pathological craniocervical junction with anabnormal clivo-axial angle in flexion, wherein upon full flexion theincrease in the tangent arc creates a deformative strain of about 0.2,which is associated with loss of function in in vivo and in vitromodels.

FIG. 40 shows the Grabb-Oakes measurement, the perpendicular distancefrom the BpC2 line (basion to posterior inferior C2 body) to the dura.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT(S)

For illustrative purposes, the principles of the present invention aredescribed by referencing various exemplary embodiments. Although certainembodiments of the invention are specifically described herein, one ofordinary skill in the art will readily recognize that the sameprinciples are equally applicable to, and can be employed in othersystems and methods. Before explaining the disclosed embodiments of thepresent invention in detail, it is to be understood that the inventionis not limited in its application to the details of any particularembodiment shown. Additionally, the terminology used herein is for thepurpose of description and not of limitation. Furthermore, althoughcertain methods are described with reference to steps that are presentedherein in a certain order, in many instances, these steps may beperformed in any order as may be appreciated by one skilled in the art;the novel method is therefore not limited to the particular arrangementof steps disclosed herein.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural references unless thecontext clearly dictates otherwise. Thus, for example, reference to “aneurological disorder” may include a plurality of neurological disordersand equivalents thereof known to those skilled in the art, and so forth.As well, the terms “a” (or “an”), “one or more” and “at least one” canbe used interchangeably herein. It is also to be noted that the terms“comprising”, “including”, and “having” can be used interchangeably.

For purposes of the present invention, “clivo-axial angle”, as usedherein refers to the angle between the dorsal aspect of the clivus andthe dorsal aspect of the axis, i.e. C2 vertebra. Also known as theclivo-vertebral angle, clivus spinal angle, and clival canal angle, theclivo-axial angle is a surrogate measurement of the neuraxis andreflects the concomitant angulation of the neuraxis, i.e. curvature ofthe neuraxis, resulting from abnormalities of the craniocervicaljunction and a central component of the measurement of brainstem stress.A normal clivo-axial angle is about 165°±about 10° in the neutralposition and about 155°±about 10° when fully flexed, reflects a normalrelationship between the cranium and the spine, and therefore a normalalignment of the central nervous system, or the neuraxis, i.e. brainstemand spinal cord. This angle becomes more acute in the presence ofplatybasia, basilar invagination, retroflexed odontoid, and functionalcranial settling. The presence of a relatively acute clivo-axial angle,for example an angle less than about 140°, results in deformativestresses within the neuraxis.

For purposes of the present invention, “neuraxial angle”, as used hereinrefers to the angle between the medulla oblongata and upper spinal cord.The neuraxial angle and clivo-axial angle are directly related such thatthe neuraxial angle decreases as the clivo-axial angle decreases. Anormal neuraxial angle is about 170±about 10 in the neutral position andabout 165±about 10 when fully flexed.

For purposes of the present invention, “basal angle,” angle between thefloor of the anterior fossa and the clivus. In normal adults, the basalangle is about 116°±about 6° and about 114±about 5° in children. As thebasal angle increases (becomes more flattened), the clivo-axial anglebecomes more pathological.

As referred to herein, “neurological disorder” refers to anyneurological disease, neurological illness, neurological condition,neurological behavior, and/or any symptom related thereto. Additionally,as used herein, a method for “treating neurological disorders” refers toany method for preventing, mitigating, reducing the incidence of,improving the condition of, improving a symptom associated with, curinga neurological disorder or combinations thereof. Exemplary neurologicaldisorders that may be treated using the method of the present inventionmay include but is not limited to: cortical motor function disorders,such as spasticity, paresis, clones, and hyperreflexia; cortical sensoryperception disorders, such as vestibular function disorders, balance andcoordination disorders, dizziness, gait problems, dyslexia, clumsiness,development delay, audition discrimination and modulation disorders,delayed and mechanical speech disorders, vision problems, eye movementand coordination disorders, and sensory disturbance disorders; lowercranial nerve dysfunctions, such as lack of coordination between speech,swallowing and smooth articulation; bowel function disorders, such asgastro-esophageal sphincter control problems; abnormal urinaryfunctioning, such as enuresis, bedwetting, and urinary bladder controldisorders; respiratory dysfunctions, such as excessive snoring,obstructive or central apnea, and abnormal respiratory response tooxygen and carbon dioxide levels; sleep-disordered breathing, such assleep apnea, muscular dysfunction, and sudden infant death;developmental disorders, such as Chiari Malformation and congenitaldiseases, such as Down's Syndrome, Morquio's syndrome,spondyloepiphysial dysplasia, achondroplasia, and osteogenesis;neurological behavioral disorders, such as attention deficithyperactivity disorder, psychological problems, including anxiety,bipolar disorder, scizophrenia, and depression, autism spectrumdisorders, including autism, Asperger Syndrome, and pervasive behavioraldisorders—not otherwise specified; anatomic conditions, such asplatybasia, retroflexed odontoid, basilar invagination, and foramenmagnum stenosis; acquired bone-softening conditions, such as Rickets,Paget's disease, and hyperparathyroidism; and metabolic bone disorders;connective tissue disorders, including hypermobility connective tissuedisorders, such as Ehlers Danlos Syndrome; cervico-medullary syndrome;renal, metabolic, and endocrine syndromes. The invention may also beused to treat autonomic neural function disorders that cause abnormalblood flow to the skin, abnormal sexual response, GERDS, dyspraxia,idiopathic scoliosis, headaches, neck pain, back pain, head pain,encephalomyelopathy in the setting of trauma, neoplasm, positionalorthostatic tachycardia, and bulbar findings.

As used herein, “neurological behavioral disorder” refers toneurological damage, deformity, condition or disease affecting behavior,emotion, memory and cognition. Individual diagnosed with a neurologicalbehavioral disorder may have emotional and/or behavioral disturbancesand may exhibit significant behavioral excesses or deficits.

As used herein, “cranio-vertebral instability” refers to conditionsinvolving the abnormal movement between the cranium and the atlas oraxis and results in abnormal biomechanical deformative stress of thebrainstem, cranial nerves and upper spinal cord. It generally arises asa result of ligamentous laxity, trauma or cancer. Cranio-vertebralinstability is characterized by: (1) one or more of the followingradiographic findings: a clivo-axial angle of about 135° or less, basionto odontoid displacement of about 1 cm or more; anterior displacement ofthe basion of about 12 mm or more from the posterior axillary line; andradiological findings used to delineate basilar invagination, such asthe odontoid rising above Wackenheim's line, the odontoid rising aboveMcGregor's line, the odontoid rising above Chamberlain's line, orbasilar invagination determination by the Johnell Redlund technique; (2)headache and/or neck pain; (3) two or more of the following symptomsand/or signs of neurological dysfunction pertaining to the brainstem andspinal cord: imbalance, vertigo, dizziness, sensory change, such aschanges in vision or eye movements, respiratory dysfunction, sleepapnea, autonomic dysfunction, such as positional orthostatictachycardia; gastrointestinal dysfunction, such as irritable bowlsyndrome; scoliosis, genit-urinary dysfunction, syringomyelia, and otherbulbar symptoms set forth in Table 2.

As used herein, “hypermobility connective tissue disorder” refers to acollagen disorder that results in hypermobility of the craniocervicaljunction and spine, ribs and appendicular joints. Exemplaryhypermobility connective tissue disorders may include Ehlers DanlosSyndrome.

As used herein, the term “spinal stabilization” may refer to any systemor method for stabilizing the craniospinal junction and/or any otherportion of the spine. In an exemplary embodiment, spinal stabilizationmay refer to any system or method for spinal and/or craniospinalalignment, spinal and/or craniospinal adjustment, correction of anyspinal and/or craniospinal deformity or a combination thereof. Anexemplary spinal stabilization system or method may involve fixation ofthe occipitocervical junction or fixation of one or more vertebra.

The present invention relates to a novel system and method for spinalstabilization. In an exemplary embodiment, the invention is directed toa system for stabilizing the craniospinal junction and a method fortreating an abnormal neuraxial angle or clivo-axial angle as well as awide variety of neurological disorders that may arise from theimposition of abnormal biomechanical stress and/or strain on thebrainstem. The technology of the present invention may be predicatedupon: reducing spinal deformities, particularly deformities at thecraniospinal junction, which in an exemplary embodiment may beaccomplished by correcting the relationship between the cranium andspine, and thereby normalizing the shape and geometry of the brainstemand spinal cord. This geometry may be described by the angulationbetween skull and spine (the clivo-axial angle), or the inherent anglebetween the medulla oblongata and spinal cord (the medullospinal angle).The present invention minimizes the invasive nature of the surgicalprocedure and provides sufficient surface area and milieu to render thesurface conducive to fixation or osteointegration. This may beaccomplished in part by increasing the available bone surface area forfixation and/or by applying a load to a bone graft. Furthermore, usingnovel surgical tools, such as a triple screw, posterior attachmentdevices, oblique trajectory instruments and trans-vertebral drills, thespinal stabilization system and method of the present invention mayminimize surgical exposure and complications, resulting in a shortersurgery with fewer risks in comparison to conventional procedures.Consequently, the invention may decrease the risk of morbidity and theduration of a patient's hospital stay.

Referring now to the drawings, wherein like reference numerals designatecorresponding structure throughout the various views, and referring inparticular to FIG. 1, an exemplary embodiment of spinal stabilizationsystem 100 of the present invention may include a bone scaffold system200, a plate 300, a connection system 400 and a vertebral attachmentsystem 500. In another embodiment, spinal stabilization system 100 mayinclude a trans-vertebral stabilization system 600, osteointegrationapparatus 700 and cranial attachment system 900. Spinal stabilizationsystem 100 may be designed for a wide variety of applications andtherefore include any combination of the aforementioned components.Spinal stabilization system 100 may be modular and/or modified for usein a wide variety of spinal stabilization applications. In an exemplaryembodiment, it may be used to surgically fuse the occipito-cervicaljunction and/or treat a neurological disorder by minimizing oreliminating abnormal biomechanical stresses of the central nervoussystem and/or any deformities of the neuraxial angle.

Bone Scaffold System

Spinal stabilization system 100 may include a bone scaffold system 200that may enhance fixation, osteointegration and/or load bearingcapabilities of spinal stabilization system 100. This system may includeone or more scaffold members 212, 214 that may facilitate fusion betweenspinal stabilization system 100 and biological tissue, such as avertebra and/or cranium. Additionally, the scaffold members may furtherconnect various components of spinal stabilization system 100 and/ormultiple biological tissues.

Scaffold members 212, 214 may have any structural configuration andmaterial composition to facilitate fixation, osteointegration and/orload bearing capability of one or more components of spinalstabilization system 100. In the exemplary embodiment of FIG. 1, bonescaffold system 200 may include one or more scaffold members 212, 214that are at least partially porous and have a large surface areasuitable for osteointegration. These scaffold members 212, 214 may besecured between any anatomical tissue, such as a vertebra or cranium,and one or more components of spinal stabilization system 100, such asplate 300, flange 325, connection system 400 and/or vertebral attachmentsystem 500. The scaffold member 212, 214 may have a thickness thatsubstantially spans the distance between a biological tissue and asurface of a spinal stabilization system 100 component such that thescaffold member 212, 214 may be tight secured therebetween. A componentof spinal stabilization system 100 may apply a compressive force againstthe scaffold member 212, 214 such that the scaffold member issubstantially positioned in continuous contact with or otherwise tightlyheld against an anatomical tissue. In an exemplary embodiment, thescaffold member 212, 214 may have a thickness of about 1 cm². Thescaffold member 212, 214 may further have a length that spans one ormore spinal vertebrae and/or spans the distance between the cranium andone or more spinal vertebrae.

A first scaffold member 212 and a second scaffold member 214 mayfacilitate the support, positioning and fixation of connection system400 to portions of the spine and/or cranium. The first scaffold member212 may have a first portion 220 that is positioned and biased againstat least one portion of a vertebra so as to promote osteointegration andfusion therebetween. Similarly, the second scaffold member 14 may have afirst portion 222 that is positioned and biased against at least oneportion of a vertebra so as to promote osteointegration and fusiontherebetween. First portions 220, 222 may be fused to any vertebrae. Forpurposes of spinal cranial fixation, in one embodiment, first portions220, 222 may be fused to at least one portion of the cervical vertebra,preferably, a portion of the C1 vertebra and/or C2 vertebra. As shown inFIG. 1, the scaffold members cooperate with plate 300, flange 325 andvertebral attachment system 500 to enhance the fixation of connectionsystem 400.

Scaffold members 212, 214 may further include one or more additionalportions that enable fusion with other vertebrae and/or portions of thecranium to facilitate spinal stabilization. In an exemplary embodiment,scaffold member 212, 214 may include second portions 216, 218 that arepositioned and biased against at least one portion of the cranium so asto promote cranial bone fusion and osteointegration.

As is shown in FIG. 2, the second portion 218 of second scaffold member214 is preferably positioned within the graft accommodation space 332defined by the flange 325 so that the inner surface 330 of the plate 300is biased to provide compressive pressure against second scaffold member14. This compression will facilitate bone fusion between the secondscaffold member 14 and the cranium. As shown in FIG. 1, the secondportion 216 of the first scaffold member 212 is similarly positionedwithin the graft accommodation space 332 and impressively biased againstthe cranial bone to promote bone fusion. Plate 300 may be fabricated soas to include more than one graft accommodation space 332, so that eachof the two scaffold members 212, 214 could be separately positionedwithin different spaces 332 defined by separate regions of the innersurface 330 of the plate 300.

Bone scaffold system 200 may be fabricated from any suitablebiocompatible material that facilitates osteointegration, osteogenesis,fixation or a combination thereof. The scaffold members 212, 214 may bebone grafts that are harvested from another part of the patient's body,such as a rib, grafts from a cadaver, or a material that is constructedand arranged to facilitate the growth of bone. The invention isaccordingly not limited to bone, but may use bone substitutes ornon-osseous materials to accomplish long-term fixation of the cranium tothe spine. For example, the scaffold members 212, 214 may be fabricatedfrom a metallurgically bonded porous metal coating that is constructedand arranged to encompass and contain bone graft material, such as thematerial that is marketed under the trade name TRABECULAR METAL™ byZimmer Inc. of Warsaw, Ind.

The scaffold members 212, 214 may alternatively be fabricated from abone forming material such as a bone substitute having a collagen baseand containing bone forming materials, or bone enhancing chemicals. Thusa bone forming material could be embodied as a fabricated mesh thatfunctions as a bone conductor (that a form into which bone growth wouldoccur, or as a bone-like medium such as coralline hydroxyapatite, whichserves as an osteoconductor for blood vessel formation and subsequentdeposition of bone, which could be injected or poured into the spacebetween the bones to be fused.

Alternatively, the scaffold members may be fabricated from a metallicmesh-like substance that encourages or enables bone growth, such astantalum mesh, which could be molded to fit into the space between theocciput and the spine, a bone allograft or a xenograft.

Plate

Spinal stabilization system 100 may include one or more plates 300 thatfacilitate spinal fixation, facilitate osteointegration and/or minimizewear and inflammation. Plate 300 may have any shape, size orconfiguration suitable for fixation to any bone structure. For example,plate 300 may be ovoid, rectangular, polyhedral or may have any shapecomprising a composite of straight and curved edges. In an exemplaryembodiment, plate 300 may be preformed to conform to a surface of one ormore spinal, cranial or facial bones. Alternatively, plate 300 may bemodular such that the shape of plate 300 may be manipulated to conformto a surface of a bone.

As shown in the exemplary embodiment of FIGS. 1-2, plate 300 may be amonolithic cranial plate sized and configured to enable secure fixationof the cranium to one or more vertebrae. The surface of plate 300 may beslightly curved to correspond to a surface of the cranium. In anexemplary embodiment, plate 300 may be further configured to define aspace 332 for accommodating one or more osteogenic materials,particularly bone scaffold system 200. As shown in FIG. 2, space 332 maybe at least partially positioned between plate 300 and the cranium. Asbest shown in FIGS. 1-2, plate 300 may include one or more edges 326, anouter surface 328 and an inner surface 330. Edge 326 may be curved andplate 300 may have a low profile so as to have no substantially sharpedges or protuberances in order to minimize wear, inflammation andstresses fractures. In an exemplary embodiment, edge 326 may havethickness of about 1 mm to about 1 cm. Additionally, plate 300 may varyin thickness along various regions of its body. For example, at leastportion of edge 326 may be about 1 mm while the central portion of plate300 may gradually increase in thickness to about 15 mm. Plate 300 mayfurther include a plurality of perforations 334 to facilitate the growthof blood vessels within the newly formed bone tissue. Perforations 334may be uniform or may vary in size and shape. These perforations 334 maybe positioned in one or more regions or throughout the entire body ofplate 300. In an exemplary embodiment, perforations 334 may have adiameter of at least 400 microns. A portion 348 of the outer surface 328of the plate 300 may be grooved in order to accommodate instrumentation,as will be described in greater detail below.

Plate 300 may be composed from any biocompatible material having thematerial and mechanical properties suitable for bone fixation and loadbearing applications. The material may be non-porous, porous or includeporous and non-porous regions. In an exemplary embodiment, plate 300 maybe at least partially porous and may be constructed and arranged toencompass and contain bone graft material, such as TRABECULAR METAL™.Additionally, plate 300 may be composed of a biocompatible material thatis either chemically inert or may induce osteointegration. Exemplarymaterials may be metals, metal alloys, ceramics, polymers, such as apolymer from the polyaryl ether ketone family (PAEK), such aspoyetheretherketones (PEEK) or polyether ketone ketone (PEKK),bio-absorbable compounds, bone, bone substitutes or a combinationthereof. Preferably, the material may include a metal alloy, such asstainless steel and/or titanium. In an exemplary embodiment, one or moreregions of plate 300, such as inner surface 330 and outer surface 328,may be composed of and/or coated with the same or different materials.In an exemplary embodiment, inner surface 330 may be composed of and/orcoated with a material that promotes bone fusion, such as anyconventional bone growth promoting substances. Optionally, the surfaceof plate 300 may be treated to adjust its frictional, wear orbiocompatibility properties. In one embodiment, at least one portion ofplate 300 may be coated with a material, shaped and/or textured to limita range of motion of plate 300 relative to a cranial surface and/or oneor more components of cranial stabilization system 900. At least onesurface of plate 300 may be optionally coated with a material capable ofenhancing, accelerating and/or promoting osteogenesis and/or promotebone fusion. In an exemplary embodiment, plate 300 may optionally have ametallurgically bonded porous metal coating, such as osteointegrationapparatus 700.

Plate 300 may further include one or more flanges 325 that may beintegrally formed with or subsequently attached to plate 300 tofacilitate fixation and/or osteointegration. Flange 325 may alsofunction to incorporate, enclose or provide a fulcrum in which a bonescaffold system 200, bone graft materials or bone substitutes may beheld for the purpose of achieving a bone union or other permanent rigidor non-rigid attachment between the cranium and the spine. By entrappingthe bone forming substances or other structural members in close unionwith the underlying cranium, flange 325 may facilitate morphogenesisthrough application of load; that is, through pressure and stabilizationof the bone forming substances to enhance the milieu favoring new boneformation. In an exemplary embodiment, flange 325 may serve to provide anon-osseous or osseous union between the cranium and spine. Thus flange325 thus may have both a physiological function and a mechanicalfunction.

While an exemplary embodiment of flange 325 may have curved surfaces andedges as well as an unobtrusive low profile that conforms to an anatomiccontour flange 325 may have any suitable shape, size, configuration ormaterial composition that would facilitate fixation and/orosteointegration. Exemplary flanges 325 may be ovoid, rectangular,cubical, box-like or polyhedral in shape. In one embodiment, flange 325may be curved and constructed to have a low profile suitable for beingpositioned over the cranium of an asthenia child where the thickness ofskin and muscle contraindicate thickness of construct. In anotherexemplary embodiment, flange 325 may be a larger box-like adaptation foradolescences or adults, designed to facilitate the incorporation ofrectangular, synthetic bone-forming substances or other non-osseouscompounds. It is thus envisioned that flange 325 may have a plurality ofconfigurations suitable for a wide variety of applications and mayconform to different anatomical morphologies.

Flange 325 may be a preformed structure having a shape that correspondsto a bone surface. Alternatively, flange 325 may be a modular structurecapable of being mechanically altered in shape to conform to ananatomical surface and/or compress or retain a bone graft material.Furthermore, flange 325 may have a non-porous structure, include one ormore porous regions or may be an entirely porous structure with aplurality of perforation 334 to facilitate osteointegration. Theperforations 334 may be uniform or different in size and/or shape so asto create a mesh-like construction that allows in-growth of bodilytissue or blood vessels. In one embodiment, flange 325 may have bothporous and non-porous regions, wherein the porous region may be aboutmore than 15% of the area of plate 300.

As shown in FIG. 1, flange 325 may be positioned adjacent to an edge 326and/or centrally positioned in plate 300. Additionally, flange 325 maybe partially or completely surrounded by or incorporated within plate300 so as to create a substantially continuous and low profilestructure. In an exemplary embodiment, flange 325 may have a thicknessof about 0.5 to about 5 mm thickness.

In one embodiment, flange 325 and/or plate 300 may partially orcompletely cover a cranial defect, such as a hole in the cranium causedby trauma, disease or craniotomy, wherein screws may be placed in flange325 and/or plate 300 rostral to the cranial defect. In an alternativeembodiment, screws may be placed along a perimeter of the cranial defectas well as a perimeter of flange 325 and/or plate 300. For example,flange 325 and/or plate 300 may be configured to substantially span thewidth of the occiput, wherein the screws may be placed on either side offlange 325 and/or plate 300 and allow screw purchase on either side ofthe occiput to accommodate the situation where a central part of theocciput has been removed, for example, as a result of an occipitalcraniotomy.

Flange 325 may also at least partially define a boundary of space 332,as shown in FIG. 2. In an exemplary embodiment, flange 325 may have anelevated contour that arises from a caudal edge 326 of plate 300 awayfrom the cranium so that space 332 forms a tunnel with one or more openends. Flange 325 may arise from any portion of plate 300, including alower, a central, an upper and/or a side region of plate 300. In anexemplary embodiment, flange 325 may rise from a region of plate 300 indirect contact with the cranial bone for a distance that is more thanabout 5 mm. The elevation of flange 325 exposes the underlying cranialbone surface, making this surface available for fusion to the overlyingbone graft. The elevation may be sized to allow placement of a bonescaffold system 200 or a sufficient amount of bone graft materials orbone substitutes adequate to provide stability for growth. In anexemplary embodiment, rib grafts may be placed between plate 300,specifically flange 325, and the patient's occipital plate to achievesuperior fusion and stability. This use and placement of these ribgrafts facilitates and expedites implantation of the spinalstabilization system, such that surgical insertion may be completedwithin a few hours, preferably about 2 hours or less. As shown in FIG.2, the inner surface of flange 325 is substantially parallel to andspaced apart from the cranium, defining a graft accommodation spacebetween the inner flange surface and the cranium when the plate 300 hasbeen secured to the cranium. It is envisioned that malleable, orwoven-bone forming substrates could be used to promote fusion, orprovide the scaffolding itself for fusion. Conversely, other materialscould be used beneath the flange 325 to provide non-osseous, non-rigidfixation.

The flange 325 may be constructed from any suitable material tofacilitate fixation or osteointegration. In one embodiment, flange 325may be composed of the same material as a portion of plate 300.Alternatively, flange 325 may be composed of a different material thanplate 300. Plate 300 and/or flange 325 may include one or more apertures336, 338, 340, 344, 346 that receive fastener 42 to enable fixation ofplate 300 and/or flange 325 to a bone and/or one or more fastenerassemblies 462, 464 to connect plate 300 and/or flange 325 with one ormore components of spinal stabilization system 100, such as support rods450, 452. A plurality of apertures 336, 338, 340, 344, 346, 372 may bearranged in any formation, such as clusters, arcs or lines, contiguouslyoriented, positioned in disparate locations, randomly positioned,uniformly positioned, overlying one another or a combination thereof. Inone embodiment, one or more of these apertures 336, 338, 340, 344, 346,372 may be placed around an edge or perimeter of the flange 325 and/orplate 300. The apertures 336, 338, 340, 344, 346, 372 may also bepositioned on a flat or curved surface of plate 300. Additionally, theseapertures may be reinforced with extra thickness to secure attachmentand may further be threaded, partially threaded or free from threads. Inone embodiment, two or more apertures may have a different size, shapeor dimension designed to engage with different fasteners 42, which maybe any device that enables fixation, such as a threaded component, hook,latch, pin, nail, wire, tether, or combinations thereof. Exemplaryfasteners 42 may include a screw, rivet, bolt, triple screw 70 orcombination thereof.

In an exemplary embodiment, one or more centrally positioned apertures340, when coupled with fastener 42, will serve to anchor plate 300and/or flange 325 to the cranium. A central aperture 340 may lieapproximately in the midline of the patient's body and cranium in orderto permit placement of fastener 42 into the thickest part of the skull,which usually runs from the inion to the opisthion. Centrally positionedapertures 340 may be threaded, partially threaded or not threaded. Oneach side of the midline, additional apertures 336, 338, 344, 346, 372which may also be treaded, partially threaded or not threaded, can bepositioned to receive fastener 42.

When coupled to centrally positioned aperture 340, fastener 42 mayprovide a primary attachment of plate 300 and/or flange 325 or to theskull. In this embodiment, fastener 42 may be a robust, corticallythreaded screw of variable length, preferably having a month within arange of about 7 mm to about 12 mm. The screw preferably has a thicknesswithin a range of about 2 mm to about 10 mm, with a blunted end. It mayhave an optional spiral lock feature that locks the screw into plate 300and/or flange 325. The screw may also be optionally lagged to provideincreased loading pressure on plate 300 and/or flange 325. In anexemplary embodiment, the screw may be made of titanium alloy, of bone,or of a bone forming or bone compatible substance. For example, aceramic, or hydroxyl-apatite composite or metal alloy/bone compositecould be used.

In an alternative embodiment, when inserted in centrally positionedaperture 340, fastener 42 may be a screw/rivet that enables rapidapplication. The screw or screw/rivet would preferably have torquestrength of greater than 35 inch lb and generate sufficient pulloutstrength to prevent dislodgement from the cortex. The screw orscrew/rivet would be placed near the middle of plate 300, and befashioned to pass through the centrally positioned aperture 340 on plate300. As shown in FIG. 3, a unique drill guide 800 may be used to guide apower drill to prepare holes in and/or insert fasteners 42 into thecranium or other bone structure for anchoring a surgical instrument,such as plate 300 and/or flange 325, thereto.

Drill guide 800 may enable angled insertion of a fastener 42 relative tothe site of insertion, as shown in FIG. 4, to ensure secure attachmentof any component of spinal stabilization system 100, including anycomponent of plate 300, connection system 400, vertebral attachmentsystem 500, transvertebral stabilization system 600, osteointegrationapparatus 700 and cranial clamp 900, to an anatomical surface as well asto minimize the surgical exposure and risks associated with spinalstabilization procedures. In particular, FIG. 4 shows the insertion of afastener 42, namely triple threaded screw 70, through a screw flange ofthe occipito-cervical spinal stabilization system and received in anoblique screw hole such that triple screw 70 is positioned oblique tothe occiput. In an exemplary embodiment, drill guide 800 may be coupledto and conform to a curved anatomical surface so as to enable theinsertion of a fastener 42 in an oblique direction thereto. Becausedrill guide 800 enables angled insertion of fastener 42 without creatinga large incision, surgical risk and recovery time is minimized. Thedrill guide 800 may be used to insert any fastener 42 into any bone orsoft tissue structure, including a vertebra and the cranium. As shown inFIG. 5, by inserting the fastener 42 at an oblique angle to the site ofinsertion, a greater length of the fastener 42 may is available foranchoring to and engaging an anatomical structure than would have beenavailable if inserted perpendicular to the insertion site. Consequently,drill guide 800 creates a stronger and more secure attachment betweenfastener 42 and the anatomical structure to which it is anchored.

In the exemplary embodiment shown in FIG. 3, drill guide 800 has a guidebody 802 defined by a lower surface 806, upper surface 808 and sidewalls810. Guide body 802 may have any size, dimension or configurationsuitable to guide and facilitate angled insertion of fastener 42 to ananatomical structure. Exemplary configurations may include arectangular, square, pyramidal, spherical or domed structure. Similarly,lower surface 806, upper surface 808 and side walls 810 may have anysuitable size, dimension or configuration, including a rectangular,square, triangular, circular or elliptical shape.

Lower surface 806 of guide body 802 may have a curved or multiplanarsurface designed to conform to one or more contours of an anatomicalsurface, such as a bone surface. Exemplary anatomical surfaces mayinclude any spinal or cranial surface, particularly any surface of thecranium or vertebra. Preferably, drill guide 800 may have a graduateddepth with a slanted lower surface 806. For example, FIGS. 3 and 6 showa lower surface 806 of drill body 802 that is positioned on and conformsto the curvature of the occiput to enhance gripping and prevent slippageof drill guide 800 during use. In an exemplary embodiment, the lowersurface 806 may be sufficiently malleable so as to enable a surgeon tomold and conform lower surface 806 to any anatomical surface; guide body802, however, should remain substantially rigid in order to guide adrill bit and maintain its structural integrity and configuration duringdrilling so as to enable the steady insertion of a fastener 42 at apredetermined angle.

As shown in FIG. 5-6, drill guide 800 may further include one or moreguide fasteners 804 positioned on a portion of the lower surface 806 tofacilitate placement of drill guide 800 on an anatomical surface. Guidefasteners 804 function to removably secure drill guide 800 to ananatomical surface, preferably a bone surface, so as to cause little tono trauma during attachment or upon removal. Exemplary guide fasteners804 may include teeth, hooks, barbs, ridges, latches or an adhesivemeans. Guide fasteners 804 may be positioned anywhere along lowersurface 806, preferably along a perimeter, edge, corner, central regionor combination thereof. In one embodiment, guide fasteners 804 may beconfigured as protuberances, such as teeth, hooks or barbs, that areextend from and are positioned at the corners and/or intermittentlyalong an edge of lower surface 806. In an alternative embodiment, guidefasteners 804 may be configured as a ridge like protuberances thatextends from and along one or more edges, preferably two or more edgesof lower surface 806.

As shown in FIGS. 5-6, an upper surface 808 of the guide body 802 mayinclude one or more apertures 812 that extend through drill guide 800for receiving a drill bit and/or fastener 42. Additionally, drill guide800 may also include one or more support structures 814 that extendupwards from upper surface 800 and may be configured as a tube likestructure aligned with apertures 812 to further guide drill bit and/orfastener 42. In one embodiment, support structure 814 may besubstantially rigid and linearly aligned with aperture 812, whereinaperture 812 and/or support surface 814 is substantially perpendicularto upper surface 808 of guide body 802. In one embodiment, drill guide800 may include two or more, three or more or a plurality of apertures812 and/or support structures 814 that have an assortment of differentangles relative to upper surface 808, ranging from about 45° to about90°, so as to enable oblique insertion of a drill or fastener 42relative to the site of insertion. Multiple apertures 812 and/or supportstructures 814 may further allow for the simultaneous drilling and/orinsertion of two or more fasteners 42.

Guide body 802 further includes a plurality of sidewalls 810, each ofwhich may have the same or different heights. In one embodiment, one ormore sidewalls 810 may vary in height along the length of the sidewall.In the embodiment shown in FIG. 5, drill guide 800 may have at least twosidewalls 810 of different heights to conform to a curved surface suchthat guide body 802 has a graduated depth along its length and/or widthand a substantially level and horizontal planer upper surface 808. Thedifference in height between two or more sidewalls 810 creates a slopedlower surface 806 of about 4° to about 40°, preferably about 15° toabout 20°. Therefore, when drill guide 800 is placed on a curvedanatomical surface, wherein aperture 812 and/or support body 814 issubstantially perpendicular to upper surface 808, a drill that passestherethrough will be inserted either at an acute, obtuse or obliqueangle relative to the site of insertion, preferably at an angle of about10° to about 45°, more preferably about 15° to about 30°.

As shown in FIG. 3, drill guide 800 may further includes a rigid handle807 integrally or removably attached to a surface of the guide body 802to facilitate orientation of drill guide 800 as well as to maintainplacement of drill guide 800 during drilling or insertion of fastener42. Handle 807 has a hand grip region 809 connected to an elongatedshaft 811 that may be integrally formed with or removably attached to anupper surface 808 or sidewalls 810 of guide body 802. Alternatively,shaft 811 may be removably inserted in or integrally formed within asurface of guide body 802 defining aperture 812 and/or support structure814. When configured to enable removable attachment, a distal end ofelongated shaft 811 may include a handle fastener that may be coupled toone or more corresponds guide body fasteners. Exemplary handle fastenersand corresponding guide body fasteners may be hooks, latches, notches,male fasteners, or female fasteners. Preferably, a plurality of guidebody fasteners may be positioned on an upper surface 808, a side surface810, an interior surface of guide body 802 defining aperture 812, aninterior or exterior surface of support structure 814, or combinationsthereof.

Connection System

Spinal stabilization system 100 may further include a connection system400 that functions to connect the various components of spinalstabilization system 100 to enable a wide variety of spinalapplications, such as rigid fixation. Connection system 400 may bemodular so as to accommodate and enable fixation of a plurality ofdifferent spinal stabilization components that may be oriented in a widevariety of different orientations. In the exemplary embodiment of FIG.1, connection system 400 may include one or more support rods 450, 452and one or more fastener assemblies 462, 464, 402, 404, 406, 408.

As shown in the exemplary embodiment of FIG. 1, connection system 400may be operatively associated with the apertures 336, 338, 340, 344, 346of plate 300 and/or flange 325, which may be configured as pre-drilledthreaded mounting holes 336, 338, 340, 344, 346, 372 to facilitateattachment of plate 300 and/or flange 325 to one or more components ofspinal stabilization system 100, such as vertebra attachment system 500and cranial attachment system 900. In an exemplary embodiment, one ormore support rods 450, 452 may pass through one or more perforation 334in plate 300 and/or flange 325 to connect to the triple screw, either byinserting a support rod 450, 452 through a hole 69 defined in the triplescrew 70 or by inserting the triple screw 70 through a hole 468 definedin a support rod 450, 452. Alternately, plate 300 and/or flange 325 mayhave a groove, a pop-out section or may have a region that possesses thefaculty of perdurability to allow passage of the stabilization elementconnecting cranium to spine. This configuration may be advantageous inlowering the overall profile of the rod, thereby minimizing thepotential deformity of overlying tissue.

In an exemplary embodiment, first portions 454, 458 of first and secondsupport rods 450, 452 may be connected to plate 300 and/or flange 325 bymeans of first and second fastening assemblies 462, 464, respectively.The plate 300 therefore preferably includes manifold screw holes inorder to permit the support rods 450, 452 to be secured to the plate 300and locations that are most suitable for an individual patient. Secondportions 456, 460 of the first and second support rods 450, 452 aresecured to the cervical spine of the patient, as will be described ingreater detail below. As shown in FIG. 1, fasteners 42 and fastenerassemblies 462 engaged in plate 300 and/or flange 325 may serve toanchor stabilization elements, such as rods, plates or other structures,of spinal stabilization system 100.

The first and second support rods 450, 452 provide the main structuralconnection between the cranium and the upper cervical spine during theimmediate postoperative period. Support rods 450, 452 are preferablystandard titanium rods, approximately of about 3-4 mm gauge, bent toconform to the correct craniospinal angle. The salient distinguishingfeatures of support rods 450, 452 relative to other rods currentlyavailable are two-fold. The first is bending rods 450, 452 at an γ anglereflecting the corrected reduction of the angle between the cranium andthat of the spine, as shown in FIG. 12; in the preferred embodiment,this will be pre-set, thus introducing a bend in the rod having anangle, γ, within a range of about 70° to about 90°, preferably about 75°to about 90° to achieve an obtuse angle of preferably about 110° toabout 90°, more preferably about 105° to about 90°, between the occiputof the cranium and the posterior lamina of the cervical vertebra, asshown in FIG. 2. Accordingly, the first and second support rods 450, 452are contoured to ensure a postoperative craniospinal relationship thatconfers a clivo-axial angle (the angle between the dorsum of the secondcervical vertebra and the dorsum of the clivus) approaching about 145°to about 165°, and more preferably about 155° to about 165°.Simultaneously, the degree of ventral brainstem compression should berendered close to zero, by virtue of the reduction of angulation betweenthe cranium and spine, and in some cases by the posterior translation ofcranium upon the spine.

Second, the craniospinal support rods 450, 452 will have apre-established rise option (the β rise, FIG. 12), to accommodate thenon-linearity of the level of the posterior ring of the first cervicalvertebra C1 to the surface of the lamina of C2 and lateral mass of C3.Accordingly, the presence of the pre-established β rise will allow thesupport rods 450, 452 to contact the C1 and C2 laminae.

In an alternative embodiment shown in FIGS. 7( a)-(b), connection system400 may include an articulating rod system having one or morearticulating support rods 470, 472 that may be attached to a cranial andvertebral surface as well as to one or more components of spinalstabilization system 100, including one or more components of plate 300,cranial attachment system 900, vertebral attachment system 500 orcombinations thereof. Each of first and second articulating support rods470, 472 may have one or more rod members 474, 476, 478, 480 configuredas conventional rigid spinal rods suitable for load bearingapplications. Additionally, articulating support rods 470, 472 may beconstructed from the same material as that of the previous discussedembodiment, preferably a plastic material having an elasticcharacteristic or a carbon fiber material. These rod members may beconnected by one or more, two or more, three or more, preferably no morethan about three, articulating joints 482 to permit a limited amount ofrotational motion, lateral bending or combinations thereof. Exemplaryjoints, may include a swivel mechanism or ball and socket couplings,enable articulating support rod 470, 472 to enable limited rotation,lateral bending or combinations thereof. In the embodiments shown inFIG. 7( a), articulating joint 482 enables rotation of a first pairs ofrod members 474, 476 and second pair of rod members 478, 480 relative toone another. In an exemplary embodiment, the articulating rod systemenables up to and including about 20° of lateral bending in flexionextension mode in the sagittal plane, about 10° in each direction.Preferably, the system may enable about 10° to about 15° of lateralbending in one or both directions. The system may also enable up to andincluding about 10° of rotation and up to and including about 10° ofside to side movement, preferably up to and including about 5° of sideto side movement. Articulating support rods 470, 472 therefore may beused to facilitate spinal stabilization but does not fuse the skull andspine.

In an alternative embodiment, the articulating rod system may have abifurcated configuration such that an articulating support rod 471 thatincludes a base rod member 473 that attaches to a cranial surface, aplate 300, cranial attachment system 900 or combinations thereof andbifurcates into a first rod member 475 and second rod member 477 thatare connected to the cervical vertebrae and/or a vertebral attachmentsystem, forming a forked Y shaped configuration. In one embodiment baserod member 473 may have a larger gauge of about 4 mm to about 9 mm thanfirst and second rod member 475, 477. An articulating joint 482 connectsthe base rod member 471 to first and second rod members 475, 477 toallow for rotational motion and/or lateral bending about one or moreaxis at articulating joint 482. In one embodiment shown in FIG. 7( b),articulating joint 482 is a swivel mechanism that enables rotationalmotion about a horizontal y axis at the articulating joint 482. In thisembodiment, articulating support rod 471 may be bifurcated both at aproximal for attaching to two cranial clamps 912 and at a distal end forattaching to two different portions of a vertebra. In anotherembodiment, a ball or socket is positioned on a distal end of base rodmember 471 designed to be operatively coupled to a corresponding socketor ball that is integrally connected first and second rod members 475,477 to enable rotational and lateral bending. To enable further motion,rod members 471, 473, 475 may include additional articulating jointspositioned along the length thereof.

The articulating rod system may be used with any component of spinalstabilization system 100 of the present invention, including the variousembodiments of bone scaffold system 200, plate 300, vertebral attachmentsystem 500, cranial attachment system 900, a trans-vertebralstabilization system 600 and an osteo-generation apparatus 700.Alternatively, the articulating rod system may be used with any otherspinal stabilization system.

First and second fastening assemblies 462, 464 connect support rod 450,452 to a craniospinal surface and optionally, to one or more othersurgical instruments, such as a component of plate 300 and/or cranialattachment system 900. An exemplary first and second fastening assembly462, 464 configured as a triple screw 70 is shown in greater detail inFIGS. 8( a)-8(b). In the preferred embodiment, an unthreaded hole 468 isdefined in the first portion 454 of the first support rod 450 and athreaded hole 372 is provided in the plate 300. Triple screw 70advantageously has a first threaded portion 76 at a lower section ordistal end thereof that is constructed and arranged to be screwed intothe cranial bone 78 and a second portion 74 at an intermediate sectionthereof that is sized and pitched to mate with the threaded hole 372 inthe plate 300.

Triple screws 70 have the unique characteristic of deriving stabilityfrom fixation within the skull, the plate 300 and around the rod orplate that connects the cranium to the spine. In addition, the triplescrew 70 is tri-purposive: first, it connects the plate to the cranium;second, it screws into or fits tightly and secures the plate, third itattaches to and secures the plate to the craniospinal connectingdevices; by attaching to the skull, it eliminates plate torque aroundthe central screw 42. In so doing, it eliminates one of the steps commonto all other craniospinal devices: that of an additional and independentmeans of attaching the plate 300 to the craniospinal rod or plateconnector.

Triple screws 70 are so-called because they possess three functionalportions of the screw length: a threaded first portion 76 for attachmentto the cranial bone 78, a threaded, or non-threaded, second portion 74that may be configured to engage a first surgical instrument, such asplate 300, and a third threaded portion 80 for attaching a secondsurgical instrument, such as support rod 450. The central orintermediate first portion may be threaded to enhance binding to theplate 300, or non-threaded to allow a lag effect upon the plate 300, inorder to allow the insertion of the screw to tighten the plate down tothe cranial bone 78, depending upon the requirements of the particularstabilization. Additionally, each portion may have a different diameter,a different sized threading, or different contour, different length, orcombinations thereof that is customized to for the aforementionedfunction.

The triple screws 70 may be placed in one of many potential screw holeson each side of the plate 300, in order to accommodate to thevariability of the system that attaches the cranium to the cervicalspine. Whilst the triple screws 70 are shown in the upper portion of theplate in the illustrated embodiment, they may in another embodiment beplaced in the lower aspect of the plate. They are not limited to beingpositioned at lateral opposite sides of the plate 300, but may be placednear the middle of the plate 300. The triple screw 70 can be turned toany direction to accommodate the craniospinal rod 450, 452 or connectionsystem 400.

The triple screw 70 will preferably be inserted through the plate andscrewed into the skull. The triple screw 70 will provide increasedstability to the plate and rod system by virtue of the combined fixationof the screw within the plate and the skull. The triple screw 70 may bethreaded at the level of the skull with a cortical or cancellous thread,or could in another embodiment utilize a rivet-type fixation. In anyevent, the internal portion of the screw is firmly fixated to the skull.

Triple screw 70 further includes a third threaded portion 80 at an upperportion thereof that is sized in pitch to mate with an internallythreaded hexagonal nut 82. As is shown in FIG. 8( b), which provides atop plan view of the first fastening assembly 462 configured as a triplescrew 70, wherein an upper surface of the triple screw 70 and/or nut 82is provided with a slot 84 for receiving a screwdriver blade.

In the exemplary embodiment shown in FIGS. 9( a)-9(b), first and secondfastening assemblies 462, 464 are configured as alternative triplescrews embodiment that further includes a hole 69 defined through thewidth of triple screw 70 and below nut 82 for receiving, engaging andretaining the first support rod 450. Hole 468 may be positioned in anybody portion of triple screw 70, including the first, second and thirdportions 76, 74 and 80. As shown in FIG. 9( a), hole 69 is preferablylocated between the first and third portions 76, 80.

Additional fastening assemblies 402, 404, 406, 408 having the samestructure and configuration as first and second fastening assemblies462, 464 may connect support rods 450, 452 to spinal vertebrae and/orone or more surgical instruments, such as one or more components ofvertebral attachment system 500.

FIGS. 10-11 depict a unique tool 86 that is constructed and arranged tobe used in conjunction with the fastening assembly 462, particularlywhen configured as triple screw 70. Tool 86 includes a handle 88 and ashaft 90 that may be provided with a universal joint 92 foraccessibility purposes, e.g. to accommodate non-orthogonal placement ofthe screw. For instance, if access to the triple screw 70 is encumberedby a patient's corpulence, the screw may be inserted at an angle. Ascrewdriver blade 94 is provided at a distal end of the shaft 90 and ispreferably sized and shaped to be effectively received by the slot 84that is defined in the upper surface of the triple screw 70.Additionally, tool 86 preferably includes a sleeve 96 that is slidableupwardly and downwardly on the lower portion of the shaft 90 between afirst retracted position that is shown in FIG. 10 and a second, extendedoperative position that is shown in FIG. 11. Sleeve 96 is shaped todefine an internally threaded socket that mates with the external threadof third portion 80 of the triple screw 70. Sleeve 96 is further mountedto the shaft 90 so that it is prevented from rotating with respect tothe shaft 90. Accordingly, a surgeon may use the tool 86 in theoperative position that is shown in FIG. 10 in order to tighten thetriple screw 70 with respect to the plate 300 and the cranial bone 78with the sleeve 96 stabilizing the tool 86 with respect to the triplescrew 70 and preventing the blade 94 from slipping out of the slot 84.

Integrated Plate and Connection System

Referring now to FIG. 13, spinal stabilization system 100 of the presentinvention may be constructed according to an alternative exemplaryembodiment including an integrated fixation member 382 wherein plate 380is integral and preferably unitary with first and second appendages 350,352. The appendages 350, 352 would intimately relate to the posteriorring of C1 (the first vertebra and the lateral mass of C2, C3 and to anyof the lower vertebrae, even as low as the thoracic vertebrae). The goalof the monolithic design would be to simplify and increase theefficiency of application and stabilization of the device to thecraniospinal junction.

Plate portion 380 is preferably constructed identically to plate 300described above with reference to the previously described embodimentexcept as is described otherwise herein. The first and second appendages350, 352 are preferably rigid and in the preferred embodiment areintegral with and/or extend from a pair of generally parallel extendingrod members 450, 452. Appendages 350, 352 are preferably preformed asdescribed above with reference to the first embodiment of the inventionso as to be bent at an angle reflecting the corrected reduction of the γangle, shown in FIG. 12, between the cranium and that of the spine,which in the preferred embodiment this will be pre-set within a range ofabout 75° to about 90°, preferably about 75° to about 90° to achieve anobtuse angle of preferably about 110° to about 90°, more preferablyabout 105° to about 90°, between the occiput of the cranium and theposterior lamina of the cervical vertebra. Accordingly, the first andsecond integrated appendages 350, 352 are contoured to ensure apostoperative craniospinal relationship that confers a clivo-axial angle(the angle between the dorsum of the second cervical vertebra and thedorsum of the clivus) approaching about 145° to about 165°, morepreferably about 155° to about 165° and more preferably about 165°.Simultaneously, the degree of ventral brainstem compression should berendered zero, by virtue of the reduction of angulation between thecranium and spine, and in some cases by the purposeful posteriortranslation of cranium upon spine.

In addition, the integrated appendages 350, 352 preferably incorporate apre-established rise option (the β rise, described above with referenceto FIG. 12), to accommodate the non-linearity of the level of theposterior ring of the first cervical vertebra C1 to the surface of thelamina of C2 and lateral mass of C3. The presence of the pre-establishedp rise will allow the integrated appendages 350, 352 to contact the C1and C2 laminae, as shown in FIG. 12.

Another advantageous feature of the embodiment of the invention that isdepicted in FIG. 13 is the provision of adjustment slots 382, 384 in thefirst and second appendages 350, 352, respectively, to permit positionaladjustment of the integrated fixation member 382 with respect to thefastener assemblies 402, 404 that are used to secure the first andsecond appendages 350, 352, respectively, to the pedicle of the C2vertebrae. As FIG. 13 shows, adjustment slot 384 as well as adjustmentslot 382 may include a plurality of propositioned apertures oradjustment holes 386, 388 to permit indexing of fastener assembly 404within the appendage 352 or variability of screw purchase.

Likewise, adjustment slots 384, 382 may be provided in the respectiveportions of the first and second appendages 350, 352 that areconstructed and arranged to be secured to the C1 vertebrae by fastenerassemblies 406, 408. This portion of the appendages 350, 352 ispreferably constructed so as to be slightly flared at the C1 vertebraeto allow lateral variability.

As may be visualized from viewing FIG. 13, several possibilities oflatitude are offered for the screw heads at C1, and several options forthe screw heads of C2 are also available. The appendages 350, 352 may besolid, tubular, porous or even a metallurgically bonded porous metalcoating that is constructed and arranged to encompass and contain bonegraft material, such as the material that is marketed under the tradename TRABECULAR METAL™ by Zimmer Inc. of Warsaw, Ind.

Vertebral Attachment System

Referring now to FIGS. 14-16, spinal stabilization system 100 mayfurther include a unique vertebral attachment system 500 for positioningand biasing the second portions 220, 222 of the first and secondscaffold members 212, 214 against at least one cervical vertebral bodyof a human cervical spine so as to promote bone fusion between thecervical vertebral body and the respective scaffold member 212, 214.

In a first exemplary embodiment shown in FIGS. 14-16, vertebralattachment system 500 includes a transversely oriented vertebral plate550 that is positioned to compress the first scaffold member 212 andsecond scaffold member 214 against a vertebral body such as thevertebral body C2 that is depicted in FIG. 14. The vertebral plate 550serves several purposes. First, the vertebral plate 550 holds the graftmaterial (the bone, bone substitute or other non-osseous material) inclose contact, and usually under pressure, with the underlying spinalvertebrae, to facilitate in-growth of blood vessels or other tissue, asis dramatically depicted in FIGS. 14-15. Second, the vertebral plate 550stabilizes the two sides of the spinal stabilization system 100,connecting the respective support rods 450, 452 from one side to that ofthe other, thereby decreasing the potential for toggling.

Accordingly, the vertebral plate 550 is connected to the first supportrod 450 at one portion thereof that includes a first clamping structure552 for releasably clamping one end of the vertebral plate 550 to thefirst support rod 450. In the preferred embodiment, the first clampingstructure 552 includes a curved plate portion 556 that curves about mostof the circumference of a first support rod 450. A fastener 42,preferably configured as a screw, extends through first and second holesthat are defined in the curved plate portion 556 for tightening andloosening the first clamping structure 552 with respect to the firstsupport rod 450.

Likewise, the vertebral plate 550 is connected to the second support rod452 at a second portion thereof that includes a second clampingstructure 554 for releasably clamping a second, opposite end of thevertebral plate 550 to the second support rod 452. The second clampingstructure 554 includes a curved plate portion 558 that curves about mostof the circumference of the second support rod 452. A screw 120 extendsthrough first and second holes that are defined in the curved plateportion 558.

The curved plate portions 556, 558 of the respective clamping mechanisms552, 554 preferably extend around the circumference of the respectivesupport rod 450, 452 as viewed in transverse cross-section for anangular distance of at least three radians. In addition, the fasteners42, preferably configured as clamping screws, are preferably positionedon the medial side of the respective support rod 450, 452.

The vertebral plate 550 is preferably curved so as to be concave on aside thereof that is positioned to contact the first scaffold member 212and said second scaffold member 212.

The vertebral plate 550 further preferably includes structure forpermitting adjustment of a length of the vertebral plate 550, whereby alateral spacing distance between said first and second laterally spacedsupport rods may be adjusted. In the preferred embodiment, this isaccomplished by constructing the vertebral plate 550 out of two separatecomponents that are attachable to each other, specifically a firstcurved connector portion 564 and a second curved connector portion 566,as is best shown in FIG. 16.

The first connector portion 564 has a plurality of adjustment holes 570defined therein while the second connector portion 566 similarly has aplurality of adjustment holes 572 defined therein. A top-loadingfastener 42, preferably configured as a screw, which is best shown inFIG. 14, is provided for securing the first connector portion 564 to thesecond connector portion 566 and is preferably applied centrally in aprecise manner in order to stabilize the first and second connectorportions 564, 566. Fastener 42 is preferably although not necessarily alock screw having a snap off head. A Vernier scale option may be used togenerate the best precise fit, but other adaptations may be used, withthe most important requirement being that a secure fit is created.

The graft loading vertebral plate component arms 564, 566 are preferablycurved, and may possess a plurality of curve sizes to accommodate thespecific graft or implanted material size. In one possible alternativeembodiment, the vertebral plate arms are straight with a rise toaccommodate the underlying material.

The surgically implantable instrumentation of the spinal stabilizationsystem 100 that has been described above, including the plate 300 thesupport rods 450, 452 and the vertebral plate 550 may alternatively befabricated from a bioabsorbable material that progressively loses itsstrength and mass over time as it is absorbed into the human body. Theideal bioabsorbable material would have a composition that would retainsufficient strength for a sufficient period of time for adequate bonefusion and bone mass to develop so that the first and second boneforming material based structural members 212, 214 would provideadequate structural strength to maintain the fusion of the humanoccipitocervical junction at all times and under all foreseeablecircumstances.

In a second exemplary embodiment shown in FIGS. 17-22( c), vertebralattachment system 500 may include at least one vertebral clamp 512, atleast one vertebral fastener 522, and at least one vertebral plate 510configured to be securely fastened to any vertebra of the spinal column.Vertebral attachment system 500 may be designed such that vertebralclamp 512 and vertebral fastener 522 securely anchor vertebral plate 510to a portion of a vertebra, as shown in FIG. 17. Vertebral plate 510 inturn may be connected to other Orthopedic structures and assemblies. Inan exemplary embodiment, vertebral attachment system 500 may bestructurally configured to enable attachment to a posterior region ofvertebra and may be able to withstand at least normal spinal loads. Itis envisioned that the system of the present invention may be compatiblewith any orthopedic structure or assembly to enable spinal stabilizationbetween vertebrae and/or enable stabilization of the occipitocervicaljunction.

Vertebral clamp 512 may have any structure, dimension, configuration orgeometric shape suitable for gripping, clasping, clipping or otherwiseretaining a portion of a vertebra so as to enclose, surround and retainan upper, lower and side surface of a vertebra. In one embodiment, atleast one portion of vertebral clamp 512 conforms to a surface of avertebra. Preferably, vertebral clamp 512 may be sized and shaped tosurround a posterior region of a vertebra. As shown in FIGS. 18(a)-18(b), vertebral clamp 512 may include a curved surface having acircumference of approximately 4 radians that encircles an upper, lowerand side portion of the posterior arch of the C1 vertebra. In anexemplary embodiment, vertebral clamp 512 may have at least two members,a first member 505 for engaging an upper surface of a vertebra and asecond member 506 for engaging a lower surface of a vertebra that isseparated by a space sized to accommodate a portion of vertebra. Firstand second members 505, 506 may be opposed and spaced apart from oneanother in a parallel or V shaped configuration. Vertebral clamp 512 mayalso include a third member 507 that connects first and second members505, 506 so as to abut and engage a side surface of the posterior archto further facilitate the retention of vertebra. As shown in FIG. 18(a), vertebral clamp 512 may have a U, semi-circular or collar likeshape. Preferably, vertebral clamp 512 is configured to be sufficientlythin and have a low profile such that it does not substantiallyobstruct, compress or impinge any adjacent vertebral components. In analternative embodiment, first and second members 505, 506 may have thesame structure and configuration as first and second members 905, 906 ofcranial clamp 912 shown in FIG. 23( c).

In an exemplary embodiment, at least one aperture 508 may be defined invertebral clamp 512 for receiving vertebral fastener 522. The innersurface of aperture 508 may be smooth, partially threaded or completelythreaded; aperture 508 may also include bevels, collars, insets or anyother structure that would facilitate the retention of vertebralfastener 522. In an exemplary embodiment, vertebral clamp 512 mayinclude a plurality of apertures 508, preferably two or more pairs ofapertures 508 defined in first and second members 505, 506. Preferably,at least one aperture 508 defined in a first member 505 may begeometrically aligned with an aperture 508 defined in a second member506. Apertures 508 of vertebral clamp 512 may have a variety ofdifferent sizes and shapes to accommodate different vertebral fasteners522.

Vertebral clamp 512 may be fabricated from any high strength andbiocompatible material. In an exemplary embodiment, vertebral clamp 512may be fabricated from any material having sufficient material andmechanical properties that would enable load bearing applicationsincluding spinal stabilization. The material used to fabricate vertebralclamp 512 may include a biocompatible metal, metal alloy, ceramic,polymer, such as a polymer from the polyaryletherketone family (PAEK)family, such as polyether ether ketone (PEEK) or polyether ketone ketone(PEKK), or composite material. Preferably, the material may include ametal alloy, such as a titanium alloy. Optionally, the surface ofvertebral clamp 512 may be treated to adjust the frictional, wear orbiocompatibility properties of vertebral clamp 512. In an exemplaryembodiment, at least one portion of vertebral clamp 512 may be coatedwith a material, contoured, and/or textured to limit a range of motionof vertebral clamp 512 relative to the vertebra and/or vertebral plate510. In another embodiment, vertebral clamp 512 may be coated with amaterial to minimize wear of vertebral clamp 512 and/or facilitateosteointegration.

Vertebral attachment system 500 may include any number of vertebralclamps 512 to attach vertebral plate 510 to a vertebra. In an exemplaryembodiment, a sufficient number of vertebral clamps 512 may be attachedto a vertebra to enable spinal stabilization applications. Preferably,the system may include at least about one to three vertebral clamps 512,more preferably, about two to three vertebral clamps 512.

As shown in FIGS. 18( a)-18(d), vertebral fastener 522 may removablysecure vertebral clamp 512 to a vertebra. Vertebral fastener 522 may beany element that is compatible with vertebral clamp 512 and vertebralplate 510 so as to enable load bearing applications, such as spinalstabilization. In an exemplary embodiment, vertebral fastener 522 mayhave the same configuration as fastener 42 and/or fastening assembly462. Vertebral fastener 522 may have any suitable dimension,configuration or geometric shape. In an exemplary embodiment, vertebralfastener 522 may include a threaded component, hook, latch, pin, nail,wire, tether, or combinations thereof. Preferably, vertebral fastener522 may be sized and shaped to secure vertebral clamp 512 to a posteriorregion of a vertebra. Vertebral attachment system 500 may include aplurality of vertebral fasteners 522 having different configurationsand/or dimensions compatible with vertebral clamp 512 and vertebralplate 510.

Vertebral fastener 522 may be fabricated from any material suitable forsecuring vertebral clamp 512 to a vertebra. In an exemplary embodiment,vertebral fastener 522 may be fabricated from any high strength andbiocompatible material. The material used to fabricate vertebralfastener 522 may include a biocompatible metal, metal alloy, ceramic,polymer, such as a polymer from the polyaryl ether ketone family (PAEK)family, such as polyether ether ketone (PEEK) or polyether ketone ketone(PEKK), or composite material. Preferably, the material may include ametal alloy, such as titanium.

Optionally, vertebral fastener 522 may also include a lock 509 tofurther secure the retention of a portion of a vertebra. Lock 509 may beany mechanism that ensures that vertebral fastener 522 is securelyattached to vertebral clamp 512, vertebral plate 510 and/or a vertebra.Lock 509 may also have any suitable dimension, configuration orgeometric shape and may be fabricated from any suitable material. In anexemplary embodiment, lock 509 may be a threaded component, hook, latch,pin, nail, wire, tether, or combinations thereof.

In an exemplary embodiment, lock 509 may be threaded component, such asa screw, bolt, rivet, or nut. As shown in FIG. 19, lock 509 may be a nutcoupled to the head of vertebral fastener 522. Vertebral fastener 522may be secured by preventing it from being unscrewed or otherwisedetached from vertebral clamp 512, vertebral plate 510 and/or a vertebrawithout first removing the nut. In one example, to remove the nut, itmust be turned in the opposite direction in which a threaded vertebralfastener 522 must be turned to detach vertebral fastener 522.

As shown in FIGS. 18( a)-20, in one exemplary embodiment, vertebralfastener 522 may be a threaded component, such as a screw, rivet, orbolt. Preferably, vertebral fastener 522 may be a triple screw thatpossesses three functional portions along the length of the screw: athreaded portion for attachment to bone; a threaded or non-threadedportion to engage vertebral plate 510, and a threaded or non-threadedportion to engage vertebral clamp 512. Each portion may have a differentdiameter, a different sized threading, or different contour, differentlength, or combinations thereof that is customized to for theaforementioned functions. The triple screw may provide increasedstability by virtue of the combined fixation of the screw withinvertebral plate 510, vertebral clamp 512 and the vertebra. Triple screw70 further includes a threaded portion at an upper portion thereof thatis sized in pitch to mate with an internally threaded hexagonal nut 82that may be used to retain another surgical instrument, such as asupport rod 450, 452. For example, triple screw 70 may engage a supportrod 450, 452 either by inserting the triple screw 70 through a holedefined in the body of support rod 450, 452 or by inserting the supportrod 450, 452 through a hole 468 defined in the body of triple screw 70.In one embodiment, the hole 468 positioned in the triple screw 70 may bepositioned below nut 82 and arranged in any body portion of the triplescrew 70, preferably between the threaded portion for attachment to boneand the threaded portion for engaging with nut 82. The threadedcomponent may have a small diameter, for example, about 1.5 mm to about4 mm and a length of about 6 to about 20 mm. Vertebral fastener 522 maycouple vertebral clamp 512 to a vertebra by penetrating a portion of avertebra and vertebral clamp 512 at the dorsal and/or ventral apertures508. Vertebral fastener 522 may also include a lock 509, such as a nut,that prevents loosening under applied physiological loads. In theexemplary embodiment shown in FIG. 18( a), the tip of vertebral fastener522 does not extend substantially past ventral aperture 508 of vertebralclamp 512 so as to injure the vertebral artery, vertebral vein, spinalnerve roots and/or spinal cord.

In the alternative exemplary embodiment of FIG. 18( d), vertebralfastener 522 may be located adjacent to but does not penetrate thevertebra. In this embodiment, vertebral fastener 522 extends throughvertebral clamp 512 at the dorsal and/or ventral apertures 508, andsecures a vertebra by functioning as a clasp or latch, passing adjacentto the vertebra. Because vertebral fastener 522 does not penetrate thevertebral body, this embodiment minimizes trauma and vertebra erosion.When vertebral fastener 522 is a triple screw, the length of the screwthat extends adjacent to the vertebral body may optionally benon-threaded in this embodiment. As discussed above, vertebral fastener522 may also include a lock 509 to prevent loosening under appliedphysiological loads.

Vertebral fastener 522 may be used to attach vertebral clamp 512 to anyportion of a vertebra that would enable load bearing applications, suchas spinal stabilization. In exemplary embodiment, vertebral clamp 512and vertebral fastener 522 may be attached to a posterior region of avertebra, preferably at a location sufficiently distanced from thevertebral artery, vertebral vein, spinal nerve roots, spinal cord or acombination thereof to minimize the risk of possibly severing,compressing, impinging, or otherwise injuring the aforementioned spinalcomponents. In an exemplary embodiment, vertebral clamp 512 andvertebral fastener 522 may be attached to the posterior arch of the C1vertebra. Vertebral clamp 512 and vertebral fastener 522 may also beattached to a posterior region, such as the spinous process, pedicle orlamina, of the lumbar vertebrae, thoracic vertebrae, sacrum vertebrae,or coccygeal vertebrae. FIG. 20 shows vertebral attachment system 500attached to a posterior region of an upper level thoracic vertebra,wherein a translamina screw engages the spinal canal by penetrating thecancellous and/or cortical bone of a vertebra to secure vertebralattachment system 500. The same vertebral attachment system 500, withminor modifications, may be similarly located on any cervical, thoracicor lumbar vertebrae.

As shown in FIG. 21( a), vertebral attachment system 500 of the presentinvention may further include at least one modular vertebral plate 510that may be attached to vertebral clamp 512 and a vertebra usingvertebral fastener 522. Vertebral plate 510 functions as a scaffold thatmay be fastened to and stabilize one more other orthopedic structure,including spinal stabilization assemblies. Vertebral plate 510 mayoptionally be used to also position and bias a bone graft material, suchas bone, a bone substitute or other non-osseous material, into closecontact with and/or under pressure against, at least one vertebra so asto promote bone fusion.

Vertebral plate 510 may have any configuration, shape or dimension thatmay be compatible with vertebral clamp 512 and vertebral fastener 522and that may enable load bearing applications, such as spinalstabilization. In an exemplary embodiment, the system may include aplurality of vertebral plates having different dimensions,configurations and sizes that may be customized to different vertebralregions or application. As shown in the exemplary embodiment of FIG. 21(b), vertebral plate 510 may be curved along a portion of its body thatmay correspond to the curved surface of the C1 vertebra's posteriorarch. Preferably, vertebral plate 510 may be sized and/or shaped tocomplement a posterior region of a vertebra. As shown in FIG. 17,vertebral plate 510 may be a thin curved plate having at least onedimension that is approximately the same as that of a vertebra.

Vertebral plate 510 may also be elevated or extended to accommodate anenlarged vertebra caused by expansion duroplasty or an increased spinalcanal size. In an exemplary embodiment, vertebral plate 510 may furtherinclude structure for adjusting a length of vertebral plate 510, wherebya lateral spacing distance between said first and second laterallyspaced vertebral fastener 522 may be adjusted. In a preferredembodiment, this may be accomplished by constructing vertebral plate 510out of two separate components that are attachable to each other,specifically a first connector portion 564 and a second connectorportion 566, as is best shown in FIG. 16. The plurality of apertures570, 572 in vertebral plate 510 may be used to adjust the firstconnector portion 564 relative to the second connector portion 566. Afastener 42 may be provided for securing the first connector portion 564to the second connector portion 566 and is preferably applied centrallyin a precise manner in order to stabilize the first and second connectorportions 564, 566. Fastener 42 may be a threaded component, hook, latch,pin, nail, wire, tether, or combinations thereof. In an exemplaryembodiment, fastener 42 is a threaded component, such as a rivet, boltor screw, preferably a lock screw having a snap off head. A Vernierscale option may be used to generate the best precise fit, but otheradaptations may be used, with the most important requirement being thata secure fit is created. Vertebral plate 510, including connectorportions 564, 566 may be loaded with graft material and may be contouredor sized to accommodate the specific graft or implanted material size.In one possible alternative embodiment, the connector portions may becurved or may be straight with a rise to accommodate the anatomy of thevertebra and/or the application of any bone graft material.

Vertebral plate 510 may be coupled to a vertebra and vertebral clamp 512any manner. In an exemplary embodiment, vertebral plate 510 may includeone or more apertures 520 that may be compatible with vertebral fastener522 and/or other orthopedic structures. Apertures 520 may be arranged inany manner along the body of vertebral plate 510. By incorporating aplurality of apertures 520 spread out along vertebral plate 510,vertebral attachment system 500 may support or connect to othervertebral attachment systems 500 and/or other orthopedic structuressituated in various different locations. Additionally, apertures 520 mayhave a variety of different sizes and/or shapes so that vertebral plate510 may be compatible with different vertebral fasteners 522 and/ororthopedic structures.

As shown in the exemplary embodiment of FIG. 17, vertebral plate 510 maybe anchored to the vertebral lamina or the posterior arch of a C1vertebra by inserting vertebral fastener 522 through aperture 520 ofvertebral plate 510, a portion of a vertebra and the dorsal and/orventral apertures 508 of vertebral clamp 512. Vertebral plate 510 may belocated between vertebral clamp 512 and a vertebra. Alternatively, asshown in FIG. 19, vertebral clamp 512 may be located between vertebralplate 510 and a vertebra.

Vertebral plate 510 may be fabricated from any high strength andbiocompatible material. In an exemplary embodiment, vertebral plate 510may be fabricated from any material having sufficient material andmechanical properties for load bearing applications, such as spinalstabilization. The material used to fabricate vertebral plate 510 mayinclude a biocompatible metal, metal alloy, ceramic, polymer, such as apolymer from the polyaryl ether ketone family (PAEK) family, such aspolyether ether ketone (PEEK) or polyether ketone ketone (PEKK), orcomposite material. Preferably, the material may include a metal alloy,such as stainless steel and/or titanium. Optionally, the surface ofvertebral plate 510 may be treated to adjust the frictional, wear orbiocompatibility properties of vertebral plate 510. In an exemplaryembodiment, at least one portion of vertebral plate 510 may be coatedwith a material, shaped and/or textured to limit a range of motion ofvertebral plate 510 relative to the vertebra and/or vertebral clamp 512.In another embodiment, vertebral plate 510 may be coated with a materialto minimize wear of vertebral plate 510 and/or facilitateosteointegration.

The modular attachment system of the present invention may beoperatively assembled and customized to enable a wide variety ofapplications and to create a custom fit for each patient. For example,the attachment system may include a combination of any number ofvertebral clamps 512, vertebral fastener 522, vertebral plates 510, andconnection system 400 having any of the above discussed configurations,shapes or dimensions. Vertebral clamp 512, vertebral plate 510 andvertebral fastener 522 of exemplary vertebral attachment system 500 maybe assembled during surgery. Alternatively, as shown in anotherexemplary embodiment of vertebral attachment system 500 of FIGS. 22(a)-22(c), one or more vertebral clamp 512 and vertebral plate 510 may beprefabricated as an integral device and subsequently fastened to avertebra using vertebral fastener 522 during surgery. Any orthopedicstructure, such as a cranial and/or vertebral plate, may be fastened tothe attachment system. FIGS. 22( b)-22(c) show an occipital plateanchored to a vertebral attachment system 500, enabling stabilization ofthe occipitocervical junction.

The attachment systems of the present invention provides numerousadvantageous over spinal fixation systems of the prior art. Because theattachment system may be located on the posterior portion of anyvertebra, such as the posterior arch of the C1 vertebra, it encumbersonly the dorsal aspect of a vertebra where the major tension forcesexerted during flexion of the neck occur, and where therefore, fusion ismost retarded. Typically the posterior surface of the C1 vertebra is theleast acceptable locus of fusion because of the high shear over theposterior surface in flexion, extension and rotation; the majorloading/compression forces in extension occur on the cranial and caudalsurfaces of the C1 vertebral arch, and these surfaces are more condoningof the fusion than the posterior surface of the posterior C1 ring. Theattachment system is also advantageous because it may have a uniquestructural configuration that is: compatible with a posterior region ofa vertebra, sufficiently thin to minimize the risk of neural or spinalcord compression, and/or does not significantly weaken the vertebra towhich it is fastened. Additionally, because the attachment system mayalso be formulated as a modular kit including a plurality of vertebralclamps 512, vertebral fastener 522, vertebral plates 510 and connectionsystem 400 of varying sizes and configurations, it may be customized foreach application and/or patient. Furthermore, the attachment systemprovides an effective, fast and safe means for vertebra attachment. Inaddition to attaching to a vertebral surface, vertebral attachmentsystem 500 may also be adapted for use in anchoring one or more surgicalinstruments to any anatomical surface, particularly any bone structure.Specifically, it is envisioned that vertebral attachment system 500 maybe adapted to be attach to any cranial or craniospinal surface so as tobe used in conjunction with spinal stabilization system 100 or otherspinal stabilization system. Vertebral attachment system 500 may be usedindependent of spinal stabilization system 100. For example, vertebralattachment system 500 may be adapted to anchor one or more surgicalinstruments to a long bone.

Cranial Attachment System

Referring now to FIGS. 23( a)-23(c), spinal stabilization system 100 mayfurther include a cranial attachment system 900 that connects one ormore surgical instruments, such as one or more components of plates 300,osteointegration apparatuses 700, connection system 400 or combinationsthereof, to a cranial bone, such as the occipital plate, occiput orcalvarium. Using cranial attachment system 900, only a minimal amount ofcranial bone is necessary to anchor the surgical instruments. Cranialstabilization system 900 therefore enables a surgeon to connect one ormore surgical instruments to the cranium even when a substantial portionof the occipital plate has been removed due to a craniotomy or trauma.Cranial stabilization system 900 may be particularly suited to anchoringan upper end of one or more support rods 450 and/or plates 300 to thecranium after a suboccipital craniotomy has been performed.

As shown in FIGS. 23( a)-23(c), cranial stabilization system 900 mayinclude at least one cranial clamp 912 configured to engage a cranialsurface and at least one cranial fastener 922 that may be coupled withcranial clamp 912 and one or more surgical instruments, such as supportrod 450, plate 300, flange 325, porous member 750 or frame member 760,which in turn may be connected to or otherwise operatively associatedwith other orthopedic structures. Intended to anchor one or morecomponents of plate 300, osteointegration apparatus 700, connectionsystem 400 or combinations thereof, cranial attachment system 900 isdesigned to withstand at least normal spinal loads. It is envisionedthat the cranial attachment system of the present invention may also becompatible with other orthopedic structures or assemblies for enablingstabilization of the occipitocervical junction.

In one embodiment, cranial clamp 912 may have the same or similarstructural configuration and material construction as clampingstructures 552, 554 or vertebral clamp 512, preferably adapted to engagea cranial surface, and cranial fastener 922 may have the same or similarstructural configuration and material construction screws 122 orfastener 522, preferably adapted for engaging a cranial surface. Inanother embodiment, cranial stabilization system 900 may have the sameor similar structural components as the vertebral attachment system 500that have been adapted for engaging and/or attaching to a cranialsurface.

Cranial clamp 912 may have any structure capable of enclosing,surrounding and retaining an upper, lower and side surface of thecranium. In one embodiment, cranial clamp 912 surrounds an edge of acranial surface, such as the lower edge of the occipital plate or acranial edge defining a cranial defect. For example, cranial clamp 912may surround and enclose an edge of a hole defined in the cranium causedby trauma, disease or surgical incision. Cranial clamp 912 may have anydimension, configuration or geometric shape suitable for gripping,clasping or otherwise retaining a portion of a cranial surface adjacentto a cranial edge. In one embodiment, cranial clamp 912 has at least twomember portions, a first member 905 for engaging an upper surface of thecranial bone and a second member 906 for engaging a lower surface of acranial bone that is spaced apart from first member 905. In oneembodiment, first and second members 905, 906 are opposed and spacedparallel relative to one another. Alternatively, first and secondmembers 905, 906 may form a V like configuration. First and secondmembers 905, 906 may have any shape, dimension or configuration suitablefor positioning and engaging a cranial bone therebetween. Exemplaryconfigurations may include a discoid, rectangular, ovid, circular,square, star or triangular shape. To decrease the profile of cranialclamp 912, an exterior surface of first and second members 905, 906 issmooth, and a distal end thereof may be tapered so as to be thicker at aproximal end adjacent to a cranial edge and thinner at a distal end. Asshown in FIG. 23( b), cranial clamp 912 has three member portions, afirst and second member 905, 906 for engaging an upper and lower surfaceof a cranial bone, respectively and a third member 907 that abuts andengages the cranial edge and connects first and second members 905, 906.In one embodiment, at least one member of cranial clamp 912 conforms toa surface of a cranium, such as a curved upper surface, lower surface orside surface of a cranial edge. A proximal end of first and/or secondmembers 905, 906 adjacent to the cranial edge or third member 907 may beabout 10° to about 40°, preferably about 10° to about 30°. First andsecond members 905, 906 may have a length of about 5 mm to about 5 cm,preferably about 10 mm to about 15 mm and a width of about 3 mm to about20 mm, preferably about 5 mm to about 20 mm, more preferably, about 3 mmto about 12 mm, and most preferably, about 10 mm to about 13 mm. Firstand second members 905, 906 may have a thickness of about 1 mm to about9 mm, preferably, about 2.5 mm to about 5 mm. In one embodiment, thirdmember 907 may have the same length, width and thickness dimensions. Asshown in FIG. 23( b), cranial clamp 912 may have a U, semi-circular orcollar like shape. In one embodiment, first, second and third members905, 906 and 907 may have a low profile to avoid or minimize theoccurrence of cranial deformities that may cause pain and discomfort tothe patient.

In an alternative embodiment shown in FIG. 23( c), first and secondmembers 905, 906 each have a base member 909 connected to a plurality ofextension members 910 to enhance attachment to a cranial bone. One ormore, preferably two or more, more preferably three or more, and mostpreferably five or more extension members 910 may be extend from basemember 909 in a finger like configuration. In an exemplary embodiment,base member 909 and/or extension members 910 may have a discoid,rectangular, ovid, circular, square, star or triangular shape. In oneembodiment, extension members 910 may have different sizes, shapes anddimensions. For example, two or more extension members 910 may havedifferent lengths or direction and degrees of curvature to facilitateattachment to a cranial bone. In another embodiment, extension members910 may be sufficiently malleable to enable a surgeon to movably arrangeextension members 910 relative to one another to facilitate andcustomize attachment about a cranial edge.

One or more holes 908 may be defined in first member 905 and/or secondmember 906 for receiving cranial fastener 922. Preferably, one hole 908centrally defined in a first member 905 may be aligned with another hole908 centrally defined in second member 906. In one embodiment, cranialclamp 912 may include a plurality of holes 908 positioned at a distalend of extension members 910 as well as a central region of base member909. Cranial clamp 912 may also include a plurality of holes 908 havinga variety of different sizes and shapes to accommodate different cranialfasteners 922. The structure, contour and configuration of hole 908 maybe the same as that of aperture 508.

Cranial attachment system 900 may include any number of cranial clamps912 for attaching one or more surgical instruments to a cranial surface.In one embodiment, cranial attachment system 900 includes at least oneor more cranial clamps 912 for connecting an upper end of each ofsupport rods 450, 452 to a cranial surface. Preferably, the system mayinclude at least about 1 to 6 cranial clamps 912, more preferably, about2 to 4 cranial clamps 912. The cranial clamps 912 may be positionedequidistantly, symmetrically or asymmetrically along and about aperimeter of a cranial edge that defines a cranial defect, preferably atleast two cranial clamps 912 may be arranged on opposing sides of acranial defect. In one embodiment, one or more cranial clamps 912 may bearranged along a cranial edge that defines an upper end of the cranialdefect.

As shown in FIGS. 23( a)-23(c), a cranial fastener 922 may removablysecure cranial clamp 912 to a cranial surface and enable load bearingapplications, such as spinal stabilization. Cranial fastener 922 may beany fastener that is sized and configured to secure cranial clamp 912 aswell as one or more surgical instruments to a cranial surface. In oneembodiment, cranial fastener 922 may have the same structuralcomponents, configuration and material construction as vertebralfastener 522. Cranial attachment system 900 may also include a pluralityof cranial fasteners 922 having the different configurations ordimensions that are compatible with holes 908 that may vary in size andshape. In an exemplary embodiment, cranial fastener 922 is configured asa screw, such as a set screw.

In an exemplary embodiment, cranial fastener 922 may be a triple screw70 that possesses at least three functional portions along the length ofthe screw. The triple screw 70 may be inserted into a cranial bone, suchas the occipital plate, occiput, or calvarium, such that a firstthreaded portion is positioned within and engages the interveningcranial bone. Alternatively, the triple screw 70 can pass through thecranial bone into second member 906 of cranial clamp 912, such that afirst threaded portion engages both the intervening cranial bone and/orsecond member 906 of cranial clamp 912. A second threaded ornon-threaded portion may engage first member 905 of cranial clamp 912. Athird threaded or non-threaded portion may engage one or more surgicalinstruments. The triple screw may further include a top loadingexternally threaded portion for engaging with an internally threaded nut82. Each portion may have a different diameter, a different sizedthreading, or different contour, different length, or combinationsthereof that are customized for the aforementioned functions. In oneembodiment, a hole 468 for receiving a support rod 450, 452 is definedin the body of triple screw 70 below the nut 82. The hole 468 may bearranged in any portion of the triple screw 70, preferably between thefirst threaded portion for attachment to bone and the threaded portionfor engaging with a nut 82. In an alternative embodiment, a hole may bedefined in support rods 450, 452 through which triple screw 70 may beinserted and coupled. The triple screw 70 may provide increasedstability by virtue of the combined fixation of the screw to a surgicalinstrument, cranial clamp 912 and the cranium. In one embodiment, thethreaded component may have a small diameter, for example, about 1.5 mmto about 4 mm and a length of about 6 to about 20 mm.

Cranial fastener 922 may couple cranial clamp 912 to a cranial surfaceby passing through a portion of the cranial bone as well as a ventralhole 908 defined in first member 905 and/or a dorsal hole 908 defined insecond member 906. In one embodiment, the tip of cranial fastener 922penetrates the cranial plate, dorsal hole 908 of second member 906 andventral hole 908 of first member 905. In an alternative embodiment, thetip of cranial fastener 922 does not extend past or does not extendsubstantially past ventral hole 908 of second member 906 so as tominimize the risk of injuring the brain or spinal cord. Additionally, toprevent cranial fastener 922 from perforating the dura, the distal tipof cranial fastener 922 may be rounded so that it gently pushes away theunderlying dura when implanted in the cranium. Additionally, the lengthof cranial fastener 922 may be about 1 cm or less to further preventperforating the dura.

In a preferred embodiment, cranial clamp 912 of cranial attachmentsystem 900 may be used in lieu of plate 300 to anchor support rods 450,452 to a cranial bone. As cranial clamp 912 only requires a smallcranial surface area to anchor a surgical instrument, such as supportrods 450, 452, it may be particularly useful in circumstances wherein alarge portion of the cranium has been removed. Additionally, cranialclamps 912 also enables a surgeon to more freely arrange and anchorsupport rods 450, 452 to a cranial surface than would be possible usinga conventional cranial fixation plate. To lower the profile of thecranial attachment system 900, cranial fastener 922 may be recessedwithin cranial clamp 912, and a support rod 450 may be connected to anexterior surface of cranial clamp 912, including an exterior surface ofmembers 905, 906, 907 or combinations thereof, forming a monolithicplate. As shown in FIG. 7( a)-7(b), articulating rods are integrallyformed with an exterior surface of third member 907.

In an alternative embodiment, cranial attachment system 900 may beoperatively associated with a plate 300 and/or osteointegrationapparatus 700 as well as support rods 450, 452. For example, plate 300may be anchored to a cranial surface by inserting cranial fastener 922through one or more apertures 336, 338, 340, 344, 346 of plate 300,through the dorsal and/or ventral holes 908 of first and second members905, 906 of cranial clamp 912 and into a portion of the cranial bone.Plate 300 may be seated between an upper surface of first cranial clampmember 905 and the upper distal end of cranial fastener 922 so thatcranial clamp 912 is positioned between the cranium and plate 300.Alternatively, plate 300 may be positioned between first member 905 ofcranial clamp 912 and the cranium. In another embodiment, cranial clamp912 and cranial fastener 922 may be indirectly attached to a plate 300and/or osteointegration apparatus 700. For example, plate 300 and/orosteointegration apparatus 700 may be attached to the support rods 450,452 at one location, and support rods 450, 452 may be attached tocranial fastener 922 at another location. Similarly, plate 300 and/orosteointegration apparatus 700 may be directly attached to cranialfastener 922 and indirectly attached to the support rods 450, 452.

The modular cranial attachment system of the present invention may beoperatively assembled and customized to enable a wide variety ofapplications and to create a custom fit for each patient. For example,cranial clamp 912, cranial fastener 922 and one or more surgicalinstrument, such as plate 300 and/or support rod 450, 452, may beassembled during surgery. Alternatively, one or more cranial clamps 912and surgical instruments may be prefabricated as an integral device andsubsequently fastened to a cranial surface using cranial fastener 922during surgery.

Cranial attachment system 900 offers numerous advantages overconventional cranial fixation systems of the prior art. Whereasconventional cranial attachment devices are dependent upon the amount ofbone for anchoring, width of the craniotomy defect and thickness of theoverlying scope toward the midline, cranial attachment system 900 canengage and be positioned in multiple sites around a craniotomy defect,is not limited by bone (calvarial) thickness, and may be rapidly andsafely implanted. Furthermore, cranial attachment system 900 has a lowprofile designed to minimize pain and discomfort.

In addition to attaching to a cranial surface, cranial attachment system900 may also be adapted for use in anchoring one or more surgicalinstruments to any anatomical surface, particularly any bone structure.Specifically, it is envisioned that the cranial attachment system 900may be adapted to be attach to any vertebral or craniospinal surface soas to be used in conjunction with spinal stabilization system 100 orother spinal stabilization system. Cranial attachment system 900 may beused independent of spinal stabilization system 100. For example,cranial attachment system 900 may be adapted to anchor one or moresurgical instruments to a long bone.

Trans-Vertebral Stabilization System

In an exemplary embodiment, spinal stabilization system 100 may furtherinclude a trans-vertebral stabilization system 600 that may function tofacilitate and enhance fixation of the connection system 400 and/orvertebral attachment system 500. The trans-vertebral stabilizationsystem 600 may be designed to enhance fixation of a vertebral implant byanchoring the implant in a direction substantially orthogonal to theimplant pull-out force. In an exemplary embodiment, trans-vertebralstabilization system 600 may comprise one or more connectors 601 and oneor more connector assemblies 602. The trans-vertebral stabilizationsystem 600 of the present invention may be used in association with anyspinal stabilization system, including spinal stabilization system 100of the present invention.

The connector 601 of the trans-vertebral stabilization system 600 may beany structure having a shape, configuration, size and texture adaptedfor vertebral coupling and capable of resisting an implant pull-outforce. The connector 601 may have an elongate cylindrical or rectangularbody 603, such as a rod or plate, that spans a length of the vertebraand cooperates with one or more components of spinal stabilizationsystem 100. In an exemplary embodiment, the connector body 603 may havea length of about 15 mm to about 50 mm, preferably about 25 mm to about40 mm, and most preferably, about 30 mm to about 35 mm. Body 603 mayhave a low profile and a smooth surface area to minimize wear andinflammation. Portions of connector 601 may also be threaded, ribbed orinclude other mating features to facilitate coupling with the connectorassembly 602, enable penetration of or anchoring to a vertebra and/orfacilitate osteointegration with a vertebra. In an exemplary embodiment,connector 601 may be splined, so as to include grooves or other contoursin the surface of the connector 601 to facilitate vertebral fixation.Connector 601 may be fabricated from any biocompatible material having acompressive strength and elastic modulus capable of resisting orwithstanding the pull-out force of a vertebral implant. Exemplarymaterials may include titanium, composite metals, carbon fibers, PEEK ora combination thereof.

In the exemplary embodiment of FIGS. 24( a)-24(c), connector 601 may bea rod that penetrates a portion of the vertebral body, such as thespinous process or lamina. The rod may include a distal end 604 thattapers to a point. The distal end 604 and/or at least a substantiallength of the rod may be threaded to facilitate penetration and/orpassage into the vertebra. A notch 605 may be located adjacent to thedistal end 604. After the rod is inserted into the vertebra, aconcentrated force may be applied to notch 605 to break distal end 604from the rod. A proximal end 606, distal end 604, and portion of the rodadjacent to distal end 604 may be blunted, smooth, splined, threaded ormay include mating features to facilitate engagement with one or moreconnector assemblies 602.

Optionally, as shown in FIGS. 25( a)-25(b), a guide plate 607 maysurround the portion of the vertebra penetrated by the connector 601.Guide plate 607 may include apertures 608 arranged to position, receiveand support connector 601. Guide plate 607 may function to providestructural reinforcement to and further anchor spinal stabilizationsystem 100 to the vertebra. As shown in FIG. 26, alternatively or inaddition to guide plate 607, one or more washers 609 may be positionedadjacent to the point where connector 601 penetrates and exits thevertebra. In an exemplary embodiment, washers 609 may have a shape thatconforms to a portion of the vertebral surface. A locking mechanism 610,such as a nut, may be fastened to the washer to prevent loosening ormovement of the connector 601 relative to the vertebra.

As shown in FIG. 27, connector 601 may further include an integral orremovably attached sprocket 611. Sprocket 611 may include a plurality ofprotrusions, grooves, indentations, notches or combinations thereof.These structures may correspond to a plurality of mating elements 612located on a cable, cord, chain or other gearing mechanism 613. A motor614 or other mechanical means may be used to drive gearing mechanism 613and rotate connector 601. The rotational driving force applied toconnector 601 may be used to penetrate and create a hole through aportion of the vertebra.

In the alternative embodiment shown in FIG. 28, the connector 601 may bea rod or plate that substantially conforms to and abuts a portion of thevertebra but does not penetrate the vertebra. Connector 601 may beconfigured so as to curve around a portion of the vertebra, such as thespinous process or lamina, which functions to anchor and furtherstabilize a vertebral implant or spinal stabilization system relative tothe vertebra. The curved portion 615 of connector 601 may abut a portionof the vertebra that provides a resistive force substantially orthogonalto the anteriorly positioned connector assemblies 602. In thisembodiment, the body of connector 601 may have a low profile thicknesswith a substantially smooth and continuous surface. Portions of the rodor plate may be threaded or may include mating features that facilitatecoupling with the connector assemblies 602.

In general, connector 601 may be positioned relatively or substantiallyorthogonal to the pull-out force direction of a vertebral implant orpull-out force direction of connector assembly 602. In one exemplaryembodiment, connector 601 may be positioned between about 45° to about135° relative to the direction of the pull-out force or a connectorassembly 602. For vertebral implants or spinal stabilization systems 100fixed in an anterior direction, as shown in FIGS. 26-27, connector 601of the present invention may be substantially orthogonally orientedrelative to the fixation means of the vertebral implant so as to anchorand enhance stabilization. Because connector 601 is positionedsubstantially orthogonal to the direction of fixation and/or pull-outforce of the vertebral implant, spinal stabilization system 100 and/orconnector assembly 602, the invention increases the stability of platesand screws in the posterior region of the spine. Furthermore,trans-vertebral stabilization system 600 opposes rotational,medic-lateral bending or distractive tendency, thereby greatly enhancingthe overall stability of the vertebral implant and spinal stabilizationsystem 100. Stability is further enhanced because rigid fixation ofconnector 601 within the spinous process and contralateral screwcoupling opposes super-inferior bending and movement. Because thepresent invention is able to successfully mitigate and/or counternon-orthogonal stresses and reduce the overall pull-out forces exertedon any given screw or fixation means, it is possible to use a widevariety of fixations means of different caliber and still maintainstabilization. For example, it may be possible to utilize screws havinglower compressive strength, smaller diameters, shorter lengths, fewerthreads, less prominent threads or a combination thereof while stillensuring spinal stabilization.

As shown in FIGS. 26-27, connector 601 may be unilaterally orbilaterally coupled to one or more connector assemblies 602 of a spinalstabilization system 100. In the exemplary embodiments of FIG. 28, theconnector assembly 602 may include at least one fastener 616, such as athreaded component, hook, latch, pin, nail, wire, tether, orcombinations thereof that may function as part of spinal stabilizationsystem 100; preferably, fastener 616 may be a threaded component, suchas a screw, rivet or bolt. Fastener 616 may be a triple screw whichpossesses three functional portions along the length of the screw: athreaded portion for attachment to bone; a threaded or non-threadedportion to engage connector 601, and a threaded or non-threaded portionto engage a system connector 617.

Fastener 616 may include a post 618 having one or more slots 619 forreceiving connector 601 and/or system connectors 617. The device may bemodular, wherein post 618 may include one or more slots 617 forretaining connector 601. The slots 619 may have different sizes and/orshapes and may also be oriented in different directions relative to oneanother to accommodate different fasteners 616 and to enable a widevariety of applications. As shown in FIGS. 29( a)-29(b), the walls ofpost 618 which form slot 619 may have a threaded outer surface which canbe coupled to a cap 620, such as a nut or top loading screw, forsecuring connector 601 within the slot 619. Alternative embodiments mayinclude a non-polyaxial head or a splined portion that fits within post618 for a tighter fit.

In an exemplary embodiment, connector assembly 602 may further becoupled to a system connector 617, which may be used to couple one ormore components of stabilization systems 100 to each other and/or toother orthopedic structures anchored to different regions of the spinalcolumn or cranium. In an exemplary embodiment, system connector 617 maybe a component of connection system 400, such as a support rod 450, 452.As shown in FIG. 26, connector assembly 602 may attach connector 601 toa system connector 617, such as a lateral mass rod. The lateral mass rodmay be attached to a vertebra above and/or below the vertebra coupled toconnector 601. In an exemplary embodiment, system connector 617 may beangled and/or contoured to enable connection with orthopedic structureslocated at different positions. Additionally, system connector 617 maybe oriented, angled, or contoured to minimize or eliminate injuries,such as ventral brainstem compression. System connector 617 may alsoinclude an optional pre-established rise option to accommodate thenon-linearity of the level of the posterior arch of the cervicalvertebrae relative to other orthopedic structures and/or otheranatomical surfaces. System connector 617 may be secured within one or aplurality of slot 619 in post 618 using cap 620.

In the alternative embodiment shown in FIG. 26, system connector 617 mayalso be separate from connector assembly 602. In this embodiment, systemconnector 617 may still be attached to connector 601 using a systemfastener 621. In an exemplary embodiment, system fastener 621 may be aflexible fitting or sleeve that fits around connector 601. Systemfastener 621 may be removably or integrally fitted and tightened about aportion of connector 601 and may be tightened with a turn screw or nut.In another embodiment, system fastener 621 may also be integral withconnector 601 and/or connector assembly 602. System fastener 621 mayinclude a fixed screw head or a flexible polyaxial screw head that wouldenable fixation of a screw, rod or other spinal stabilization device ina wide variety of orientations. In another embodiment, system fastener621 may be coupled to a lateral mass screw or pedicle screw. Systemfastener 621 may further include a system post 622 having a system slot623 for receiving system connector 617. A system lock 624 may securesystem fastener 621 within system slot 623.

Connector assembly 602 may be constructed from any high strength andbiocompatible material. In an exemplary embodiment, connector assembly602 may be fabricated from any material having sufficient material andmechanical properties that would enable load bearing applications, suchas spinal stabilization. The material used to fabricate connectorassembly 602 may include a bio-compatible metal, metal alloy, ceramic,polymer, such as a polymer from the polyaryl ether ketone family (PAEK)family, such as polyether ether ketone (PEEK) or polyether ketone ketone(PEKK), or composite material. Preferably, the material may include ametal alloy, such as stainless steel and/or titanium. Optionally, thesurface of connector assembly 602 may be treated to adjust thefrictional, wear or biocompatibility properties of connector assembly602. In an exemplary embodiment, at least one portion of connectorassembly 602 may be coated with a material, shaped and/or textured tolimit a range of motion of connector assembly 602 relative to connector601. In another embodiment, connector assembly 602 may be coated with amaterial to minimize wear and/or facilitate osteointegration.

An osteogenic bone graft material may be applied to the junctionsbetween stabilization system 100, the vertebral body and/or systemconnector 617 to facilitate bone fusion. In an exemplary embodiment,osteogenic material may include, without limitation, autograft,allograft, xenograft, demineralized bone, synthetic and natural bonegraft substitutes, such as bio-ceramics and polymers, andosteo-inductive factors. In an exemplary embodiment, osteogenic materialmay include a bone morphogenetic protein (BMP), transforming growthfactor β1, insulin-like growth factor, platelet-derived growth factor,fibroblast growth factor, LIM mineralization protein (LMP), andcombinations thereof or other therapeutic or infection resistant agents,separately or held within a suitable carrier material. Additionally,osteogenic material may also be applied partially along or completelycover any surface of connector 601, connector assembly 602 and/or anyother orthopedic structure to which stabilization system 100 is directlyor indirectly connected to promote osteoblast generation and facilitatebone fusion. The bone graft material may be placed above, below or onany surface of stabilization system 100 as well as on any correspondingorthopedic structure. In an exemplary embodiment, connector 602 may be ascaffold coated and/or impregnated with osteogenic bone graft material,the structure of which may be naturally replaced with bone over time.

The trans-vertebral stabilization system 600 of the present applicationmay be useful for a wide variety of applications to facilitate andenhance spinal stabilization by anchoring a vertebral implant in adirection substantially orthogonal to the pull-out force. In particular,it is envisioned that the invention may be particularly useful where aC2 pedicle is too narrow to receive a screw or where an encroachingvertebral artery prohibits placement of a transarticular screw throughthe facet joint or a lateral mass. Furthermore, trans-vertebralstabilization system 600 may be used in association with anystabilization system or vertebral implant to enhance stabilization andprevent loosening of vertebral implants and/or spinal stabilizationsystems 100 in the cervical, thoracic, lumbar and sacral levels.

Osteointegration Apparatus

Spinal stabilization system 100 may further include an osteointegrationapparatus 700 that promotes bone fusion. Osteointegration apparatus 700may have any shape, size or configuration suitable for a wide variety ofapplications involving tissue adhesion and/or fusion. Theosteointegration apparatus 700 may also provide attachment to softtissue, such as muscles, tendons and ligaments. In an exemplaryembodiment, the apparatus may be particularly suitable for facilitatingbone fusion, particularly with vertebrae, cranial bones, facial bones,teeth, or other parts of the appendicular skeleton.

When used as a component of spinal stabilization system 100,osteointegration apparatus 700 may function to facilitate fixationbetween one or more vertebrae and/or the cranium in order to enhancestabilization or normalization of the craniospinal junction. In theexemplary embodiment of FIGS. 30( a)-30(b), osteointegration apparatus700 may be positioned over a portion of spinal stabilization system 100,such as plate 300, flange 325, and/or vertebra attachment 100, and/orone or more biological tissues, such as a bone surface, to assistfixation and bone fusion. By enhancing spinal fusion, theosteointegration apparatus 700 may obviate the need for using deeplypenetrating screws during spinal stabilization, thereby decreasing therisk of injuring sensitive regions of the anatomy, including thevertebral artery, brainstem or nerve roots. The device is alsoadvantageous in that it can be quickly applied, minimizing the timerequired to perform a surgical procedure and may be inserted through asmall incision, thereby minimizing surgical exposure and risk.

As shown in the exemplary embodiment of FIG. 30( a), osteointegrationapparatus 700 may include a porous member 750 and a frame member 760.The porous member 750, shown in FIGS. 30( a) and 31(a), may have anyshape or configuration suitable for facilitating fixation and/orosteointegration. In an exemplary embodiment, the porous member may havea shape that at least partially or substantially conforms to a surfaceof a vertebra and/or cranium so as to facilitate attachment thereto. Inthe exemplary embodiment shown in FIG. 30( a)-31(b), which shows theposition of osteointegration apparatus 700 relative to a patient'sbrainstem 701, spinal cord 702, cinus 703, opisthion 704, suboccipitalcranium 705, anterior tubercle of the C1 vertebra 706, posterior arch ofthe C1 vertebra 707, spinous process of the C2 vertebra 708, odontoidprocess of the C2 vertebra 713, C3 vertebra 714, bifid spinous processwith muscular attachments of the C2 vertebra 719, superior natal line720, vertebral artery 723 and C2 vertebral body 724, porous member 750may at least partially contact and abut a bone surface to facilitateosteointegration. Preferably, the porous member 750 may substantiallycontact and conform to one or more bone surfaces along a substantiallength of the porous member 750. Porous member 750 may further include aplurality of perforations sized to allow for and encourages in-growthand through-growth of blood vessels and other mesenchymal tissues. Theperforations may be either uniform or may have different sizes andshapes. In an exemplary embodiment, the perforations having a smalldiameter of about 200 to about 1000 microns, more preferably about 400to about 600 microns, and most preferably about 500 microns, to enhanceosteointegration. In an exemplary embodiment, the porous member 750 mayhave a tensile strength, hardness and thickness of about to facilitatebone fusion In the region of the surface over the host fusion surface,the porous mesh may preferably have a tensile strength of about 100 toabout 5000 psi, or more preferably about 200 to about 3000 psi, closerto the range of cancellous bone; in the external surface of the porousmesh where more structural strength is needed, a tensile strength ofabout 10,000 to about 25,000 psi, and a yield strength of about 14,500psi similar that of cortical bone may be preferable.

The porous member 750 may be synthesized from any suitable biocompatiblematerial. In an exemplary embodiment, the material may include anadhesive component to facilitate bonding of the porous body with thesurrounding tissues, including bone and/or soft tissue. The material mayalso include an osteogenesis and/or osteointegration compound toencourage fusion. The material may be substantially bioresorbable so asto be biologically incorporated into the host bone structures. Thematerial may be composed of a polymethacrylate polymer that can bepremolded or molded at the time of the stabilization procedure. The polycompound, such as polymethylmethacrylate may have other compounds mixedin to facilitate attachment, antibiosis or porosity. In an exemplaryembodiment, the porous member may be any porous isomeric mesh, a mesh oftrabecular pattern that resembles the trabecular, or cancellous bone orother biocompatible material having a structure similar to cancellous(or trabecular) bone. The porous material could be fabricated frommetal, such as metallic alloys of titanium or tantalum,carbon-composite, stainless steel, cobalt-chromium, ceramic, orbiological materials such as coralline hydroxyapatite, cancellous boneor processed cortical bone. Alternatively, or in addition, the porousmember 750 may be coated with an adhesive and/or osteogenesis materialor chemical to facilitate attachment and osteointegration. Exemplarycoatings may include osteoconductive coating includes, bone morphogenicproteins, hydroxyapatite, tissue in-growth and on-growth facilitatingproteins, or glycoprotein's, or compounds or alloys of titanium,tantalum, carbon, calcium phosphate, zirconium, niobium or hafnium.

As shown in the exemplary embodiment of FIG. 30( a), osteointegrationapparatus 700 may further include one or more frame members 760 thatreinforces and strengthen porous member 750. The frame member 760 may beeither internal or external to the porous member 750 to enhancestructural rigidity or strength and may have any shape or configurationsuitable for use in securely anchoring the osteointegration apparatus700. In an exemplary embodiment, one or more portions of the framemember 760 may conform to the shape of one or more tissue surfaces. Forexample, a frame member 760 may conform to the shape and contours of oneor more vertebrae.

One or more frame member 760 may be uniformly or randomly positionedthroughout the body of the porous member 750, including along aperimeter of, over the entire surface of (as shown in FIG. 31( a)), partof the surface of or throughout the central region of the porous member750. In the exemplary embodiment of FIG. 30( a), the frame member 760may be positioned along a portion of the perimeter of porous member 750.Specifically, frame member 760 may be a continuous unitary structure issubstantially positioned along the entire perimeter of the porous body750. Alternatively, a plurality of separate frame members 760 may bearranged substantially along the perimeter of the porous member 750body. Multiple frame members 760 may be arranged in any formation thatwould be conducive to facilitating structural reinforcement andattachment of the porous member 750. In another embodiment, one or moreframe members 760 may be interspersed within porous member 750 so as tocreate a reinforcing web. In this embodiment, the frame member 760 maybe constructed from structurally enhanced filaments that are woven intothe porous member 750 body. The reinforcing web may be interwoven,superficial or added upon as a modular component.

The frame member 760 may be fabricated from any suitable high strengthbiocompatible material that provides added support and reinforcement toporous member 750 and osteointegration apparatus 700. In an exemplaryembodiment, the frame member 760 may be fabricated from titanium, carbonfiber, or a combination thereof. The material may be substantiallybioresorbable so as to be biologically incorporated into the host bonestructures.

One or more portions of the porous member 750 and/or frame member 760may support or may be coated with an osteogenic bone graft material 721to facilitate bone fusion. Exemplary osteogenic material 721 mayinclude, without limitation, autograft, allograft, xenograft,demineralized bone, malleable, cohesive, shape-retaining putty includingmineral particles, insoluble collagen fibers and soluble collagen, bonecement, polymethylmethacrylate (PMMA), calcium phosphate (CaP),demineralized bone matrix (DBM), bi-calcium phosphate matrix, plateletgel, bone sialoprotein morphogenetic protein (BMP) in a carrier matrix,patented recombinant human protein, calcium phosphate-based materials,methomathactuloid, cranial plast, calcium-sulfate, or combinationthereof, synthetic and natural bone graft substitutes, such asbio-ceramics and polymers, and osteo-inductive factors. In an exemplaryembodiment, osteogenic material 721 may include a bone morphogeneticprotein (BMP), transforming growth factor β1, insulin-like growthfactor, platelet-derived growth factor, fibroblast growth factor, LIMmineralization protein (LMP), and combinations thereof or othertherapeutic or infection resistant agents, separately or held within asuitable carrier material and also biological agents, fleeces containingosteoprogenitor cells derived from periosteum. This material may beapplied to any surface of the osteointegration apparatus 700. As shownin FIGS. 32-33( b), it may be positioned between either a biologictissue, such as a bone surface, or other component of spinalstabilization system 100 and the porous member 750 and/or frame member750 of the osteointegration apparatus 700. Fasteners used to secure theosteointegration apparatus 700 to a biological tissue or spinalstabilization component 100 may apply a compressive force so thatosteointegration apparatus 700 and/or osteogenic material 721 may besubstantially pressed against a bone surface to facilitateosteointegration.

In addition to the porous osteointrative structure and adhesiveproperties of osteointegration apparatus 700, the apparatus may befurther fixed to a biologic tissue, such as bone, and/or component ofspinal stabilization system 100 with one or more apertures and fastener.As shown in FIG. 32, the fastener may be used to directly anchor anosteointegration to a portion of a vertebra. Alternatively, as shown inFIGS. 33( a)-33(b), the fasteners may anchor the osteointegrationapparatus 700 to a spinal stabilization system 100 component, such asvertebral attachment system 500. The fastener may serve tosimultaneously attach both osteointegration system 700 and one or morecomponents of spinal stabilization system 100, such as a vertebral clampor plate 200, to a vertebral body and/or portion of the cranium.

Porous member 750 and/or frame member 760 may include one or moreapertures 780 for receiving a fastener. The apertures 780 may havedifferent sizes and shapes and may be either placed along any surface ofthe frame member, porous member or a combination thereof. In anexemplary embodiment, the apertures may be reinforced with extrathickness to secure attachment and/or may be threaded, partiallythreaded or free from threads. The apertures 780 may be conventionallypositioned to establish a secure attachment with bone. Exemplarylocations may be in the subocciput, through the keel of the suboccipitalbone, C1 ring, C1 or C2 pedicle, C2 lateral mass, a C2 spinous processor combinations thereof. As shown in the embodiment of FIGS. 31(a)-31(b), the osteointegration system 700 may include a centralsuboccipital aperture and fastener 710, a C1 vertebra aperture andfastener 711, a C2 spinous process aperture and fastener 712, a C2lateral mass aperture and fastener 715, C2 pedicle aperture and fastener717, a C2 transarticular aperture and fastener 718 and lateralsuboccipital aperture and fastener 722. In one embodiment, the aperturemay be a transarticular screw hole that passes through a vertebralpedicle. The location of the apertures and fastener may also be selectedto avoid compressing sensitive regions of the anatomy, such as thevertebral artery 723, brainstem 701 or spinal cord 702, as well as avoidoverlapping fastener placement, which may be accomplished by using asegmentation algorithm. A CT rendering may map and/or show thepreordained placement of fasteners and/or other components of spinalstabilization system 100 on a patient's cranium and/or spine. Forexample, certain parts of the CT rendering of a pedicle would beregistered and any overlying screw position may be identified.

The fastener may be any device capable of securing osteointegrationapparatus 700 to a bone and/or portion of spinal stabilization system100, such as a threaded component, hook, latch, pin, nail, wire, tether,or combinations thereof. Preferably, the fastener may be a threadedcomponent such as a screw, bolt, rivet or nut. In an exemplaryembodiment, the fastener may have a shallow penetration depth to preventinadvertent injury to the vertebral artery, spinal cord or nerve rootswhich may induce a cerebrospinal fluid leak. Alternatively,osteointegration apparatus 700 may also include depth penetratingfastener to enhance fixation. In this embodiment, apertures may bespecifically designated and positioned for receiving depth penetratingfasteners in order to minimize the risk of injury to the vertebralartery, spinal cord or nerve roots.

In a preferred embodiment, osteointegration apparatus 700 maysubstantially conform to the patient's anatomy and/or to implanteddevices, such as spinal stabilization system 100. To accomplish this, inone exemplary embodiment, osteointegration apparatus 700 may be apreformed custom constructed from a 3D image of a CT rendering. Forexample, one or more portions of the osteointegration apparatus 700 maybe designed to conform to the anatomy of the subocciput, C1 and the C2laminae, as shown in FIGS. 30( a)-31(a), based on a pre-operativedigitized computer generated rendering of a patient's anatomy, to ensurefixation. The osteointegration apparatus 700 may be personalized tocreate a custom fit having no sharp edges.

In another exemplary embodiment, osteointegration apparatus 700 may be amodular preformed device capable of being manipulated to conform to apatient's anatomy. In one aspect, osteointegration apparatus 700 may bea flexible preformed structure that can be mechanically manipulated soas to change and/or retain a particular shape. The shape ofosteointegration apparatus 700 may signal to the surgeon whenappropriate normalization of bone relationship has occurred, and therebywhen normalization of neurological architecture has occurred. That is,the osteointegration apparatus 700 will have various preformedgeometries that require the normalization of the craniospinal angle. Inan exemplary embodiment, an angle between the clivus and the posteriorsurface of the odontoid process (the clivo-axial angle) will have beenmanipulated to achieve approximately 165°, which is the normal angle forthe population at large. Thus apparatus 700 may serve to identify insitu the correct clivo-axial angle, thus accomplishing a transformationof abnormal anatomy to normal anatomy. FIG. 30( b) shows the intrinsicangle between the cranial portion of the plate and the extensions ontothe lower vertebral surfaces. A wide variety of angles, ranging fromabout 130° to about 170°, may encompass the full spectrum ofabnormalities. The maximum correction of the clivo-axial angle is formost patients in the order of about 22°. Therefore a patient with aclivo-axial angle of about 110° could only be expected to undergo acorrection to about 130°. In another aspect shown in the exemplaryembodiment of FIG. 31( b), osteointegration apparatus 700 may becomposed of one or more segments 730 that may be independently moveablerelative to one another to facilitate modular reconstruction,adjustment, placement and/or anatomical conformation of osteointegrationapparatus 700 to a patient's anatomy. These modular segments 730 mayinclude porous members 750 and/or strong structural frame members 760.Each segment 730 may be separated from one another, for example as shownby gap 729 located between segments 730 in FIG. 31( b). Segments 730 maybe entirely separate from, may cooperate with or may overlap with othersegments 730 to facilitate fixation. In an exemplary embodiment,segments 730 may be hinge together to facilitate achievement ofconformality. For example, osteointegration system 700 may have aplurality of porous members 750 that are independent moveable relativeto one another but each individually hinged to a continuous frame member760. In an exemplary embodiment, the porous/trabecular mesh structuremay be soft enough ventrally or may contain slits in the porous body tobetter conform to contours of a bone. Additionally, each section may beeither rigid or may be flexible so as to be mechanically manipulatedduring surgery to conform to a patient's anatomy. To facilitate fusion,the patient's anatomy may further be modified by sculpting to conform tothe contours of the osteointegration apparatus 700. This ability tocreate an osteointegration structure that substantially conforms to apatient's anatomy may confer stability and strength to spinalstabilization system 100.

Method for Spinal Stabilization

A method for achieving occipitocervical fusion according to a preferredembodiment of the invention will now be described. The method of thepresent invention may be used to enable stabilization and/or fusion ofthe junction between one or more vertebrae and/or the occipitocervicaljunction of humans as well as animals. Specifically, the invention maybe used to enable spinal or occipitocervical instability due to traumaor chronic spinal conditions, such as degenerative spinal diseases,metabolic spinal diseases, congenital spinal diseases, endocrinologicalspinal diseases, neoplastic or infectious spinal diseases, or cancer.Examples of chronic spinal conditions which may be treated in part usingthe vertebra attachment system of the present invention includedegenerative diseases, such as systemic lupus erythematosis andrheumatoid arthritis, and metabolic conditions, such as osteomalacia,osteogenesis imperfecta, hyperparathyroidism, Ricket's Disease andHurler's Disease; which cause basilar invagination. Other examples ofconditions which may be assisted with the present invention may includecongenital conditions, such as Down's syndrome and Morquio's Syndrome ormiscellaneous conditions, such as Chiari Malformation, assimilation ofthe atlas, Klippel-Feil syndrome, condylus tertius, hypochordal bow,dystopic odontoideum, which may cause compression of the upper spinalcord or brainstem. The method for spinal stabilization may involve:pre-operatively scanning the region of the spine to be fused,manufacturing a customized osteointegration apparatus 700, surgicallyfusing the spine by connecting one or more vertebral attachment systemsand/or cranial plates and implanting the osteointegration apparatus 700.

During the pre-operative scanning procedure, a patient may be positionedon a computed tomographic scanning table. In an exemplary embodiment,the patient's spinal alignment and/or deformity may be corrected orotherwise mitigated pre-operatively by manipulating the cranium and/orspine using non-surgical methods. When correcting a deformity of theoccipitocervical junction, the patient's head is extended and theneuraxial and/or clivo-axial angle may then be normalized by applyinggentle traction, extension of the cranium on the cervical spine, and/orposterior translation. The patient's head, neck and/or torso may beretained in this corrected position with a brace, such as a neck brace,that may be molded to conform to the patient's correctly positionedanatomy to accomplish closed reduction of deformity. Optionally, aradiographic image of the region to be stabilized may be obtained toconfirm that the spinal alignment and/or deformity was corrected.

Subsequently, this anatomical region of the spine may be imaged using acomputerized tomographic (CT) scan, which may produce thin image slicesof about 1 mm. The images may be subsequently downloaded in any suitableelectronic format, such as DICOM, and sent to a manufacturer to create acustomized osteointegration apparatus 700 based on the anatomicspecifications of the scanned images. In an exemplary embodiment, theosteointegration apparatus 700 may be a 3-dimensional form-fittingtrabecular mesh designed to lay over the region of spinal fixationduring surgery.

In an alternative embodiment a patient's the skull and spine may besculpted to conform to a standard preformed osteointegration apparatus700 intraoperatively. During surgery, the patient's anatomy may besculpted to conform to the shape of the preformed osteointegrationapparatus 700. Subtle changes in the host anatomy may be sculpted toconform to the device, and the device in turn may be capable of beingmanipulated or shaped to conform to the patient's anatomy.

The patient may then be intubated and prepared for surgery byimmobilizing the cranium and/or torso. The patient may be firstpositioned prone with a Mayfield pin headrest in an appropriate sterilesurgical environment. The posterior cranium (subocciput) will then besurgically exposed.

The suboccipital bone will then preferably be lightly drilled orsculpted in order to create a flat and even surface for the positioningof the plate 300. The plate 300 will then be aligned with the long axisof the patient's body and will be positioned symmetrically about themidline axis, so that the central screw hole 340 is preferably bisectedby the midline axis of the patient's cranium as viewed in rearelevation. The center of the central screw hole 340 will then be markedon the cranium, and the plate 300 will be removed.

A central hole will then be surgically drilled in the cranium,preferably to a depth of 5-10 mm. using a high speed drill, then by aconventional surgical hand drill to complete the drilling, preferably toa total depth of between about 8 mm to about 12 mm. The screw hole willbe tapped to a depth that is about 1 mm. longer than the screw to beused. (For example, for a 10 mm screw, tap to 11 mm depth). The plate300 will then be repositioned on the midline.

The central hole may be obliquely angled and may be created by thepreviously discussed novel drill guide 800. For example, as shown inFIG. 3, the drill guide platform may be positioned on the occiput,approximately 3 cm above the opisthion. After positioning, drill guide800 may be temporarily secured to the bone surface by taping its teethinto the bone with a tamp. Because drill guide 800 may include one ormore angled drill bit receiving apertures and/or angled drill supports,a power drill may then be received by drill guide 800 to create anobliquely angled holes. Consequently, a greater screw length is insertedin the bone than would be had the aperture been oriented perpendicularto the bone surface, thereby enhancing fixation and screw purchasestrength. This enhanced fixation therefore obviates the need for bonestruts, structural bone, bone matrix or other bone substitutes forensuring secure fastener attachment. The drill guide 800 may be used tocreate obliquely angled holes for receiving any fasteners of spinalstabilization system 100. Consequently, drill guide 800 may be used toposition and orient various components of spinal stabilization system100, including plate 300, flange 325 and/or vertebral attachment system.

The central cortical screw 42 will then be inserted into the tapped holeand tightened, lagging down the plate 300 to achieve solid fixation.

When there exists a cranial defect, such as wherein a substantial amountof bone that has been removed as a result of an occipital craniotomy,plate 300 and/or flange 24 may be positioned over and preferably coverthe cranial defect. In an alternative embodiment, triple screw 70 orcranial attachment system 900 may be used to engage, plate 300, flange24, osteointegration apparatus 700, support rods 450, 452 orcombinations thereof, wherein multiple cranial clamps 912 may bepositioned around the perimeter of the craniotomy defect. In oneembodiment, cranial clamps 912 may be positioned substantiallyequidistant relative to one another and/or symmetrically about theperimeter of the craniotomy defect, wherein at least one cranialfastener 922 directly engages a calvarial edge, clamp 912, plate 300 orflange 24, and a support rod. In an alternative embodiment, one or moreclamps 912 and fasteners 922 are positioned along a perimeter of thecranial defect, wherein cranial fastener 922 directly attaches tosupport rod. Clamp 912 may be used to entirely replace plate 300, orplate 300 may be separately attached to the cranium over the cranialdefect and cranial attachment system 900.

The method may involve exposing the posterior arch of the C1 and/or C2vertebrae without injuring the vertebral vein or artery in the vertebralartery sulci. Before proceeding with the operation, the surgeon maycheck the CT or MRI to ensure that there is no stenosis at the level ofthe C1 vertebra.

The left C1 and C2 fastener assemblies 402, 406 will then berespectively inserted into the C1 and C2 vertebral bodies as is bestshown in FIGS. 1 and 13.

The left pre-contoured support rod 450 is loosely positioned within thefirst clamping mechanism on 12 of the vertebral plate 550 and is securedto the left C1 and C2 fastener assemblies 402, 406.

The triple screw position for the first fastening assembly 462 that bestaligns with the pre-contoured occipito-cervical rod 450 is thenselected. The triple screw purchase selected is then drilled in thecranium. The lateral screw purchase may then be tapped if it is not beenpre-threaded. The triple screw 70 is inserted.

The same operation is performed, again choosing the most appropriateposition for the triple screw for the second fastening assembly 464.

The Mayfield headholder is then released, and an open reduction of thecraniocervical junction is performed under fluoroscopy and under directinspection. It is ensured that the abnormal angulation (kyphosis) of thecraniospinal angle, and any abnormal translation of the skull isreduced, and that there is no rotation or lateral bending and nosubluxation at lower spinal levels. The head-holder is then relocked.

The clivioaxial angle is then measured with the goal of achieving anoptimal clivioaxial angle of about 150° to about 165°.

The support rods 450, 452 are then placed into the holes in triplescrews 70 within the respective fastening assembly 462, 464 and the hexnuts 82 are placed over the screws 70 and tightened, as shown in FIGS.8( a)-9(b).

The exposed suboccipital bone, the posterior ring of C1 and the laminaand facet joints of C2 are then surgically decorticated.

The first portions 216, 218 of the first and second bone formingmaterial based structural member 212, 214 are then inserted into thegraft accommodation space 332 that is defined between the plate 300 andthe cranium, as is best shown in FIG. 2. The cephalad part of the boneforming material based structural member should be fashioned to fitprecisely and under pressure beneath the flange 325 of the plate 300. Insome embodiments, the caudal edge 326 of the plate 300 may now be bentdown towards the cranium to further compress the graft. The caudal endof the graft should lie on the decorticated C1 and C2 (and lower levelswhere indicated) dorsal elements.

The graft loading vertebral plate is then positioned to hold down, underpressure, the portions of the first and second bone forming materialbased structural members 212, 214 that are positioned over and againstthe C1 and C2 dorsal elements using the vertebral attachment system 500of FIGS. 14-15.

The fasteners 42 are then tightened and locked on the vertebral plate.

Demineralized bone matrix may then be applied to the fusion areas andmore cancellous bone may be applied to complete the fusion. A layeredwound closure is then performed conventionally over a drain.

In another embodiment, a curved instrument 544, such as a curette, asshown in FIG. 34, may be used to open the plane ventral to the posteriorarch. The same curved curette serves as a trial template for thevertebral clamp to be fitted around the posterior arch of a patient, inorder to select the most appropriately sized vertebral clamp 512 forimplantation. The selected vertebral clamp 512 may be insertedapproximately 10-15 mm on one side of the midline of the posterior archby friction fitting vertebral clamp 512 around a portion of theposterior arch. A second vertebral clamp 512 may be insertedapproximately 10-15 mm on the opposite side of the midline. Optionally,a third vertebral clamp 512 may be placed at the midline of theposterior arch. In instances where only one vertebral clamp 512 is usedto anchor vertebral plate 510 to a vertebra, vertebral clamp 512 may beinserted at the midline. Vertebral plate 510 may be inserted between theposterior vertebra and the vertebral clamps 512, as shown in FIG. 19, orplaced above vertebral clamps 512, as shown in FIG. 17. One or moreapertures 10 of vertebral plate 510 may then be aligned with one or moreapertures 508 of vertebral clamp 512. Alternatively, one or morevertebral clamps 512 and vertebral plates 510 may be constructed as anintegral device and fastened to a region that is safely distanced fromthe spinal cord, spinal nerve roots, vertebral artery and/or vertebralvein so as to avoid severing, compressing, impinging or otherwiseinjuring the these spinal components. In one embodiment the attachmentsystem may be fastened to a posterior region, such as the posterior archof the C1 vertebra, spinous process pedicle or lamina.

An osteogenic bone graft material 17, may be applied to the betweenvertebral attachment system 500 and a vertebra or portion of the craniumto facilitate bone fusion. In an exemplary embodiment, osteogenicmaterial 17 may include, without limitation, autograft, allograft,xenograft, demineralized bone, synthetic and natural bone graftsubstitutes, such as bio-ceramics and polymers, and osteo-inductivefactors. In an exemplary embodiment, osteogenic material 17 may includea bone morphogenetic protein (BMP), transforming growth factor β1,insulin-like growth factor, platelet-derived growth factor, fibroblastgrowth factor, LIM mineralization protein (LMP), and combinationsthereof or other therapeutic or infection resistant agents, separatelyor held within a suitable carrier material. Additionally, osteogenicmaterial 17 may also be applied partially along or completely cover anysurface of vertebral clamp 512, fastener 522, vertebral plate 510,and/or any other orthopedic structure to which vertebral attachmentsystem 500 is directly or indirectly connected to promote osteoblastgeneration and facilitate bone fusion. As shown in FIG. 22( c), bonegraft material 517 may be placed above, below or on any surface ofvertebral attachment system 500 as well as any corresponding orthopedicstructure.

A transvertebral stabilization system 100 may be use to enhance spinalstabilization by anchoring a vertebral implant in a directionsubstantially orthogonal to the pull-out force. In particular, it isenvisioned that the invention may be particularly useful where a C2pedicle is too narrow to receive a screw or where an encroachingvertebral artery prohibits placement of a transarticular screw throughthe facet joint or a lateral mass. The transvertebral stabilizationsystem 100 may be used in association with any stabilization system orvertebral implant to enhance stabilization and prevent loosening ofvertebral implants and/or spinal stabilization systems 200.

In one embodiment, transvertebral stabilization system 100 may beimplanted after fastener 616 is inserted into the vertebra, preferablythrough the lateral mass or on either side of the pedicle. Fasteners 616of connector assemblies 602 may be located on various vertebra,establishing the frame work of spinal stabilization system 200.Connector 601 may then unilaterally or bilaterally inserted in fastener616 of connector assembly 602. As shown in FIG. 26, connector 601 mayfit into connector assemblies 602 bilaterally, to stabilize connectorassemblies 602 transversely, and via the coupling devices,longitudinally and rotationally.

In an exemplary embodiment, connector 601 of transvertebralstabilization system 100 may penetrate a portion of the vertebral body,such as the spinous process, to secure the connector assembly 602 to thevertebra. For example connector 601 may be placed through the base ofthe spinous process, connecting and coupling the lateral mass fasteners616 bilaterally, thus conferring enhanced stability. Penetration andpassage through the vertebral body may be affected in a variety of ways.In one embodiment, cortex perforators may be used to align connector 601relative to the connector assemblies 602 and create a through holethrough the vertebral body. The blunt proximal end 606 of connector 601may be inserted into slot 619 of connector assembly fastener 616, andthe tapered distal end 605 of connector 601 may be inserted through thethrough hole of the vertebral body.

In an alternative embodiment shown in FIG. 35, forceps 625, preferably avice grip forcep, may be used to position and precisely align connector601 relative to the connector assembly 602. The blunt proximal end 606of the rod may be placed in the connector assembly fastened 616 to thelateral mass. The tapered distal end 605 of connector 601 may be forcedinto the perforated entry site of the spinous process by applyingpressure to forcep 625. Forcep 625 may be used to guide and push the rodthrough the vertebral spinous process, as shown in FIG. 35.

In another exemplary embodiment, connector 601 having a sprocket 11 maybe used to drill a hole through the vertebral body. A motor or othermechanical means may be used to drive a gearing mechanism 13, which inturn rotates connector 601. The rotating tapered threaded tip of theconnector 601 consequently penetrates and drills a hole through thespinous process. In an exemplary embodiment, drilling may occur whileconnector 601 is supported and guided by vice grip forcep 625. Vice gripforcep 625 may be used to hold, direct and advance the shaft ofconnector 601 through the spinous process.

After connector 601 is bilaterally fastened to two connection assemblies602, a top loading nut or screw may be tightened on each post 618 tosecure connector 601. System connectors 617 may then be bilaterallycoupled to connector 601 to complete the stabilization system. Forinstance, the system connectors 617 may be connected superiorly to thecranium and may engage connector 601 and/or connector assembly 602.

A method according to an alternative embodiment of the invention wouldutilize the integrated fixation member 142 that is depicted in FIG. 13.In this method, the preferred steps are preferably slightly reordered.First, placement of the screws into the lateral mass or ring or C1 andinto the lateral mass or pedicle of C2, or into the lateral masses ofthe lower cervical or thoracic vertebrae would be performed.

Second the monolithic construct including the plate portion 380 and theintegrated appendages 350, 352, which are surrogates for the rods 450and 452 described with reference to the first embodiment of theinvention, is applied over the screw heads.

Third, the craniospinal reduction is performed.

Fourth, the plate portion 380 is screwed to the skull with the centralscrew 42. The top loading nuts of fastening assemblies 406, 408 are thentightened down over the screw heads of the vertebral screws.

In all other respects, this method is identical to the method firstdescribed above.

The aforementioned spinal stabilization procedures may be minimallyinvasive only requiring a small surgical exposure. Specifically, theprocedure need only expose the portion of the vertebrae and/or craniumto be attached to the spinal stabilization system. For example, themethod for fusing the occipitocervical junction of the present inventiononly requires exposing the subocciput, C1 ring and C2 lamina. Incisionsmay be performed under fluoroscopic guidance to further minimize thesurgical aperture. Additionally, neither implantation of the spinalstabilization device of the present invention nor implantation of theosteointegration apparatus 700 requires dissection of muscles away fromthe tip of the C2 spinous process. This minimizes the injury to themuscle attachments that hold up the neck. Vertebral attachment systemsmay be placed upon the posterior ring of the C1 vertebrae to anchor theC1 vertebra, obviating the necessity of inserting C1 lateral massscrews.

Prior to implanting the osteointegration apparatus 700, the patient maybe positioned so as to normalize the angle of the skull base withrespect to the spine. This may be accomplished by applying gentletraction, extension of the cranium on the cervical spine, posteriortranslation or any other mechanical manipulation of the anatomy of thepatient. The osteointegration apparatus 700 may then orthotopicallylowered onto the stabilized anatomical region and/or spinal fixationsystem. For methods involving the fixation of the occipitocervicaljunction, the osteointegration apparatus 700 may be laid over an exposedsubocciput, C1 fixator screws and/or the prepared lamina of C2.

In an exemplary embodiment, an abrasive tool, such as a drill, may beused to sculpt a bone surface so as to create a more perfect unionbetween the osteointegration apparatus 700 and anatomy of the patient. Asheet of pressure indicator-contact paper may be placed under theconstruct device to determine what areas or points of theosteointegration apparatus 700 are not conformal and what underlyingbone may be removed or sculpted to create a substantially completeand/or continuous contact and conformality with the osteointegrationapparatus 700.

When conformality is acceptable, portions of the cranium or spine may bedecorticated to enhance osteointegration. For example, duringoccipitocervical stabilization, the suboccipital skull and the laminaeof the first and second vertebrae may be decorticated with a high speeddrill, to allow penetration of blood vessels into the osteointegrationapparatus 700 and to provide a substrate rich in bone morphogenicprotein (BMP) upon which to lay the osteointegration apparatus 700. Theosteointegration apparatus 700 may be positioned over the spinalstabilization fasteners and may be fastened directly to one or morevertebrae, cranium and/or components of the spinal stabilization system.As shown in the exemplary embodiment of FIG. 30( a), theosteointegration apparatus 700 may be laid over the C1 screws anddirectly fastened to the C1 and/or C2 vertebra. Fasteners, such asscrews, may also be placed through the osteointegration apparatus 700into the subocciput to further enhance cranial fixation. Fasteners mayalso be positioned in the C2 lamina, lateral mass or spinous process.Optionally, fasteners may also be placed through the pedicle onto thebody of C2 or through the lateral mass into the lateral mass of C1 in aC1-C2 transarticular technique.

It may be necessary to adjust the degree of extension by repeating openreduction of the craniospinal angle. Fluoroscopy may be used to confirmconformality, and adequate normalization of the neuraxial and/orclivo-axial angle. When there appears to be substantially completecontact between the osteointegration apparatus 700 and bone, lockingelements, such as C1 lock nuts, may be tightened to more fully securethe osteointegration apparatus 700.

An autologous graft and/or allograft may be placed within the centralregion, i.e. cradle, of the osteointegration apparatus 700 facilitatefusion between the subocciput, C1 and C2. Exposed surfaces of theosteointegration apparatus 700 may also be covered in morsellised graftor graft substitute.

The incision may be closed over a drain in three to four layers, and abrace may surround the surgical region for about two to four weeks inorder to allow for adhesion between the osteointegration apparatus 700and surrounding tissue, thereby enabling spinal stabilization. Becausethe osteointegration apparatus 700 facilitates adhesion andosteointegration, the need for deeply penetrating screws is obviated.

Method for Treating A Neurological Disorder by Spinal Stabilization

The present invention is also directed to a method for treating aneurological disorder that arise from abnormal deformative stress of thebrainstem and spinal cord by stabilizing the occipitocervical junctionso as to correct an abnormal deformative neuraxial stress. Exemplaryneurological disorders arising from abnormal deformative neuraxialstress may include neurological behavioral disorders, such as autismspectrum disorder, and hypermobility connective tissue disorders, suchas Ehlers-Danlos syndrome, as well as any of the other neurologicaldisorders listed in the definition section of the present application.These treatment methods may be accomplished using the spinalstabilization system of the present invention for stabilizing theoccipitocervical junction and/or a conventional spinal stabilizationsystem for stabilizing the occipitocervical junction and normalizing theneuraxial stress.

In general, abnormal deformative neuraxial stress may be caused by anabnormal neuraxial angle, abnormal flexion, ligament weakness,non-physiological movement, or any process that results in abnormalstretching of the neurons comprising the neuraxis. Without wishing to bebound by theory, amongst other biochemical changes, it is believed thatneuraxial stress and strain may cause altered permeability of Na⁺ andCa⁺⁺ channels, loss of neuronal electro-negativity and subsequent lossof conductivity.

Without wishing to be bound by theory, abnormal deformativebiomechanically induced neuraxial stress may contribute to or causeneurological disorders. Deformities at the level of the brainstem maycause pain, observed neurological deficit, and, over time, may alterneurological behavior. Specifically, deformativebio-mechanically-induced stresses at the level of the brainstem mayresult in sleep disorders, abnormal gastro esophageal function(including GERDS), vision and reading difficulties, a multitude ofbehavioral disorders, abnormal functioning of the autonomic nervoussystem, scoliosis, abnormal gait and posture, and abnormal urinary andsexual functioning. Without wishing to be bound by theory, stress due toneuraxial deformity, even in the absence of compression, may alter cellmembrane physiology and may cause a change in neurological behavior. Bymechanically normalizing the neuraxial stress on the brainstem and upperspinal cord by cranial spinal stabilization, it may be possible to treatthe neurological disorder. Therefore, by stabilizing theoccipitocervical junction so as to normalize the neuraxial stress, itmay be possible to correct abnormalities of the neuraxial angle andclivo-axial angle and thereby treat a neurological disorder. Withoutwishing to be bound by theory, neurological disorders may be geneticallylinked to or have a pathophysiological causation in relation todeformative abnormalities of the neuraxial angle and clivo-axial angle.Therefore, it may be possible to treat one or more neurologicalsymptoms, such as positional orthostatic tachycardia, dizziness, headand neck pain, sensory disturbance, and bulbar findings, caused byhypermobility of the craniocervical junction, which is induced byabnormal deformative stress.

In an exemplary embodiment, the invention is also directed to a methodfor treating a neurological disorder or physiological condition thatunderlies or otherwise contributes to a phenotypic feature or expressionin patients diagnosed with another neurological disorder, for exampleneurological disorders and/or physiological conditions that underlie theexemplary neurological disorders described in the present application,including neurological behavioral disorders, such autism spectrumdisorder and hypermobility connective tissue disorders, such asEhlers-Danlos syndrome.

Patients who have been diagnosed with or present symptoms associatedwith a neurological disorder may be examined for the presence of anabnormal deformative neuraxial stress. The patients may be subsequentlyevaluated to determine whether an abnormal deformative neuraxial stressmay be causing or contributing to their neurological disorder and/orsymptoms. The present method for treating a neurological disorder mayinvolve evaluating one or more anatomical aspects or characteristic ofthe patient's occipitocervical junction, brainstem and spinal cord, suchas the neuraxial angle, clivo-axial angle, basal angle, neuraxialstrain, neuraxial stress or combinations thereof; determining thedeformative neuraxial stress; determining the probability of whether anabnormal deformative neuraxial stress may be contributing to and/orcausing the neurological disorder based on the determined deformativeneuraxial stress; and treating the neurological disorder by stabilizingthe occipitocervical junction so as to normalize the neuraxial stress.

To evaluate the features and characteristics of the occipitocervicaljunction, brainstem and spinal cordradiographic images, such as an MRI,CT scan, CT with myelography, or x-rays of the occipitocervical junctionmay be obtained. In one embodiment, the calculation of abnormaldeformative neuraxial stress may be accomplished by using dynamicradiographs or other imaging means to measure and/or calculate thedegree of maximum stress, such as might occur in flexion of the craniospinal junction or flexion of adjacent bone members. In an exemplaryembodiment, the radiographic image may clearly show the brainstem and/orspinal cord, as well as the anatomy of the skull base and upper spine atthe occipitocervical junction. Preferably, a plurality of images showingthe length and curvature of the brainstem and/or spinal cord from avariety of different perspectives, including a dorsal and ventralperspective, may be obtained. The most advantageous view for examiningand determining the clivo-axial angle and neuraxial angle is thesagittal view of T2 weighted images in the neutral and flexed positions,centered at the craniospinal junction. Diffusion tensor imaging,cerebrospinal flow images, and spectroscopic MRI may also be ofassistance in the determination of abnormal deformative neuraxial stressinduced pathophysiology.

In one embodiment, these radiographic images may be captured by and/ortransferred to a medical imaging computational device that supports,runs and/or is controlled by a computer readable software mediumdesigned specifically to identify, calculate and/or measure one or moreaspects of the one or more anatomical features of the capturedoccipitocervical junction, brainstem and spinal cord images, such as theneuraxial angle, clivo-axial angle, basal angle, the angle between thebone members encasing the CNS, neuraxial stress, neuraxial strain,neuraxial stress and combinations thereof. The medical imagingcomputational device and software medium may be capable of calibratingthe captured images so as to enable accurate measurements and/orcalculations of various anatomical features and aspects thereof. Forexample, it may be possible to measure the length of an outsideperimeter, insider perimeter or midline of the brainstem and spinal cordas well as the width or thickness of multiple regions of the brainstemand spinal cord. The medical imaging computational device and softwareprogram may further be capable of comparing and/or mathematicallymanipulating these measurements to obtain meaningful calculations.

In one embodiment, these calculations and measurements may be used toquantitatively determine the neuraxial stress. In an exemplaryembodiment, this may be accomplished by measuring and/or calculating theclivo-axial angle, neuraxial angle, basal angle, the angle between thebone members encasing the CNS, or combinations thereof, which in turnmay be used to calculate the neuraxial stress.

In another embodiment, the medical imaging computational device and/orsoftware medium performs finite element analysis, a mathematical methodthat reduces a continuous structure into discrete finite brick elements,to compute estimates of preoperative and/or postoperative mechanicalstress within the brainstem and spinal cord, specifically neuraxialstress. Using finite element analysis, it is possible to create acomputer generated model of an individual patient's brainstem andcervical and upper thoracic spinal cord under static conditions as wellas dynamic loading and strain. The model incorporates patient-specificanatomical data, such as deformity over the odontoid process, lengthenof brainstem and spinal cord with flexion, compression of the spinalcord by a herniated disc or spur, etc. The computations derived fromthese models undergoing flexion and extension can be used to estimatethe stresses and/or strain existing within the patient's brainstem andspinal cord, specifically neuraxial stress, in the neutral, flexion andextension conditions.

Once the abnormal deformative neuraxial stress has been determined, itcan be correlated with clinical outcome indices/metrics to determinewhether the abnormal deformative neuraxial stress substantiallycontributes to and/or causes a patient's neurological disorder. This maybe accomplished by evaluating the following factors: (1) an abnormalneuraxial stress; (2) the presence of neck pain and/or headache; (3) thepresence of at least two or more bulbar findings set forth in Table 2;(4) the presence of myelopathy; (5) a finding of cranio-vertebralinstability; and (6) the presence of an abnormal neuraxial and/orabnormal clivo-axial angle. When two or more of the aforementionedfactors are present, the abnormal deformative neuraxial stress eithercontributes to and/or causes the patient's neurological symptoms and/orneurological disorder. Without wishing to the be bound by theory, it isbelieved that the degree to which the neuraxial stress contributes to orcauses the neurological disorder may be correlated with and increasewith the increasing number of identified factors and/or severity oftheir manifestation.

Without wishing to be bound by theory, it may also be possible todetermine whether an abnormal deformative neuraxial stress contributesto or causes a neurological disorder and/or will induce the developmentof a neurological disorder or a neurological symptom by evaluating theneuraxial stress alone. Specifically, an abnormal deformative neuraxialstress about 2 times the neuraxial resting stress or more, preferably,about 3 times the neuraxial resting stress or more indicates that theabnormal deformative neuraxial stress contributes to or causes aneurological disorder and/or will induce the development of aneurological disorder or a neurological symptom.

Additionally, the aforementioned methods for determining whether aneuraxial stress contributes to or causes a neurological disorder may beused to indicate whether the patient is likely to develop a neurologicaldisorder and/or neurological symptoms as a result of the abnormaldeformative neuraxial stress. A patient who has not been diagnosed witha neurological disorder may be evaluated to determine whether anabnormal deformative neuraxial stress is present and whether it willlikely induce the development of neurological disorder and/orneurological symptoms. This may be accomplished in the same manner asdiscussed above. Subsequently, the patient may be treated by stabilizingthe occipitocervical junction so as to normalize the neuraxial stress.

In another embodiment, whether an abnormal deformative neuraxial stressmay cause or contribute to their neurological disorder and/or symptomsmay be assessed by the probability of altered electro-conductivity,which may be determined based on the patient's neuraxial strain. Thismethod may involve the same steps for evaluating one or more anatomicalaspects or characteristic of the patient's occipitocervical junction,brainstem and spinal cord as discussed above.

In one embodiment, the neuraxial strain may be calculated from theclivo-axial angle, neuraxial angle, basal angle, the angle between thebone members encasing the CNS, or combinations thereof. In anotherembodiment, measurements of the length of medulla and upper spinal cordon the ventral and dorsal surface (for the fourth ventral) may be takento directly determine neuraxial strain.

The method may also involve determining the abnormal deformativeneuraxial stress and determining the neuraxial strain therefrom. In yetanother embodiment, finite element analysis may be used to determine theneuraxial strain.

Without wishing to be bound by theory, the medullospinal angle of theneuraxis, i.e. neuraxial angle, accurately reflects the deleteriousstresses within the brainstem and upper spinal cord that may cause analteration of gene expression, cell membrane physiology and neurologicalbehavior. Determination of neuraxial stress and strain which are basedon the neuraxial angle may be preferred to accurately determineneuraxial stress and strain. The medullospinal angle α, also known asthe neuraxial angle at the medullospinal junction, is that anglesubtended at the epicenter of the arc of the medulla oblongata andspinal cord, centered at the craniospinal junction (defined by McRae'sLine), and delimited superiorly by the pontomedullary junction, andinferiorly by a point in the spinal cord is equidistant from the center(McRae's Line) to the pontomedullary line (See FIG. 36). Themedullospinal angle measures the loss of linearity of the brainstem andspinal cord, and is reflective of the subsequent stress and straingenerated by the angulation of the neuraxis over the odontoid process atthe craniospinal junction. The clivo-axial angle, which measures theangle between the dorsal aspect of the clivus and the dorsal aspect ofthe axis, i.e. C2 vertebra, is a surrogate measurement reflecting theconcomitant angulation of the neuraxis resulting from abnormalities ofthe craniocervical junction, such as from basilar invagination.Secondarily, the medical imaging computational device and softwareprogram may also measure the clivo-axial angle to provide an estimate ofthe neuraxial stress and strain.

In an exemplary embodiment, a medical imaging computational device andsoftware medium may be programmed to estimate or calculate neuraxialstress and strain using a number of different methods, which includingcalculation using the algorithms provided below. Because strain andstress may occur simultaneously in multiple directions, neuraxial strainand stress may be analyzed in the x, y and z dimensions. In general,strain, c, is defined as a change in length divided by an originallength, as expressed in equation 1.ε=ΔL/L ₀  (Equation 1)

Based on this formula, in one exemplary embodiment, it may be possibleto calculate neuraxial strain by measuring the increase in neuraxialangulation that occurs in the presence of a skull based deformity,especially during flexion of the neck. Specifically, the method mayinvolve calculating the increased length of the brainstem (medullaoblongata) as compared to the normal position within the base of theskull.

According to this method, assuming that the brainstem and spinal cordsubtends a neuraxial angle, α, as shown in FIG. 36, which is subtendedat the epicenter, then the length, l, of the dorsal columns willincrease in flexion by virtue of the increased radius, r. That is, thedorsal columns, lying more distally from the epicenter are x cm moredistant from the epicenter than the anterior surface (the black line)from the epi-center, and therefore, the dorsal columns are longer by theratio of 2π(r+x)/2πr=r+x/r  Equation 2Applying the increased length of the dorsal columns/original length, thestrain c that develops with a medullary kink is given by:ε=(r+x/r)/r  Equation 3Where r is the radius of the arc subtended by the curve caused by thekyphosis of the brainstem, and where x approximates the thickness of thespinal cord (about 1 cm) or brainstem (about 1.8 cm).

Given that the medullary curve occurs both in the brainstem (about 2 cmin length) and the upper spinal cord (about 2 cm in length), then theinner surface of the curved arc is about 4 cm. An arc subtending anangle of about 57° would have a radius, therefore, equal to the lengthof the arc; or about 4 cm. Therefore, for a uniform length of theneuraxis, the radius is given by,r=α(in degrees)/57°·4 cm Equation 4and the strain is therefore given by,ε=[(α/57·4 cm)+x/(α/57·4 cm)+x/(α/57·4 cm)]/[a(in degrees)/57°·4cm]  Equation 5

Neuraxial stress may be subsequently determined based on the calculatedstrain value or may also be independently determined.

Generally, the angle between the skull base ventral and contiguous tothe brainstem and the spine ventral and contiguous to the upper spinalcord is normally in the range of about 165°+/−about 10° depending uponwhether the neck is flexed or extended. A neuraxial angle of about toabout 150° or less and/or clivo-axial angle of about 140° or less,preferably about 135° or less may indicate the likelihood of deleteriousstresses in the CNS; a computer readable software medium and medicalimaging computational device may consequently prompt a recommendation tonormalize the relationship between the concatenated bone encasingelements and stabilizing these elements so as to normalize the stressesof the CNS.

In another exemplary embodiment, neuraxial strain may be calculatedwithout measuring the neuraxial angle. A simpler means of estimating thechange in neuraxial strain may involve analyzing the relationshipbetween an inside curvature of the brainstem, i.e. the inner ventralsurface of the brainstem, and a longer outer curvature of the brainstem,i.e. outer dorsal surface of the brainstem.

As shown in the exemplary embodiment of FIG. 36, the dotted linerepresents a line of best fit through the ventral aspect of thebrainstem/spinal cord, i.e. neuraxis, and approximates the both theventral and dorsal length of the neuraxis before deformation. The solidline of FIG. 36 that runs substantially parallel to dotted linerepresents a line of best fit over the elongated dorsal aspect of theneuraxis. An approximation of neuraxial strain may be calculated bydividing the difference in the length of these lines by the length ofthe dotted best fit ventral line.

In a third exemplary embodiment, neuraxial strain can be calculated fromthe thickness of the neuraxis. Referring to FIG. 37, LF represents thelength of the dorsum of the neuraxis after stretching over a deformity,x represents the thickness of the neuraxis at the region of thedeformity, and r represents the length of the radius from the center ofthe arc of rotation of the neuraxis to the ventral surface of theneuraxis, subtended by the angle σ radians. Since the arc L_(O),subtended by one radian, is equal in length of the radius r, strain Emay be equal to the thickness of the neuraxis divided by the length ofthe radius of the arc subtended by the angle σ over the deformity, asshown in Equation 6.ε=x/r  Equation 6

With abnormal angulation of the neuraxis (medullospinal kyphosis),radius r becomes smaller and the thickness of the neuraxis at the apexof deformity becomes the dominant variable in assessing the strainacross the dorsal half of the neuraxis.

This expression of neuraxial strain may be used to determine theelectro-conductivity of a system. In general, the relationship of strainand electro-conductivity is non-linear. In the pathological range ofstrain, (that is, approximately ε=0.17−0.21) conductivity, C, decreaseswith increased strain in an exponential fashion. That is, the change, δ,of C is inversely proportional to the exponential of the change, δ, ofstrain ε. The new expression can be inserted into the expression forneuronal conduction amplitude, and other derivative equations, toreflect alteration of conduction amplitude. It is therefore possible todetermine the relationship between strain and a change in neurologicalphysiology. In a subset of patients, neurological physiology will berelated to behavior. That is to say, neurological function and behavior,at least in a subset of patients, is a function of the deformativestress across the neuraxis.

Experimental data demonstrates that neuronal conduction amplitude isrelated to strain. Allowing 100% conductance at zero strain, and zeroconduction at excessive strains (ε of >about 0.3), then conductionamplitude C can be shown to satisfy a quadratic expression that can bemost simply expressed in this format, thus:

$\begin{matrix}{C = {1 - {k \cdot ɛ^{2}}}} & {{Equation}\mspace{14mu} 7} \\{= {1 - {k \cdot \left( {x/r} \right)^{2}}}} & {{Equation}\mspace{14mu} 8}\end{matrix}$where ε is the strain of the neuraxis, x is the thickness of theneuraxis at the point of maximum deformation, r is the length of theradius to the arc of the ventral aspect of the neuraxis (See FIG. 37),and where k is a constant for a particular neuronal system that isalgebraically related to the strain at which the particular neuronalsystem ceases to conduct an impulse. K may vary, namely increase,according to rapidity of strain (See FIG. 37), frequency of strain,modulus of elasticity of the neuraxial tissue, the ambient cerebrospinalfluid pressure, and will vary up or down according to the ionic state ofthe bathing fluid (CSF), and many other factors.

Many other polynomial expressions could be used to more closelyrepresent the conduction amplitude for given conditions.

In FIG. 38, animal research has shown that conduction amplitudedecreases with magnitude of strain, and that amplitude decreases to agreater degree with the speed at which the strain is applied.

Without wishing to be bound by theory, it is believed that somebehavioral changes may be related to abnormal conditional amplitude ofspecific neural tracts within the brainstem and spinal cord (neuraxis).The probability of abnormal behavior, Φ, relates inversely to thedecrement in conduction amplitude, such that as conduction amplitudedecreases, the probability of abnormal behavior increases. The followingalgorithms may be used to calculate this probability of abnormalneurological behavior as a function of conduction and neuraxial strain.Φ=f(C)⁻¹  (Equation 9)

An aggregate of abnormal conduction amplitudes within various neuronaltracts can be related to behavior change (Φ), expressed thus:φ=(fΣ ^(n)(C)/n)⁻¹  Equation 10where n is the number of the various pertinent neural fiber tractsinherent in any behavior. For instance, articulation of speech involvesthe nucleus ambiguous fibers, fibers to the hypoglossal nucleus andponto-cerebellar fibers.

Substituting the equivalent expression for conduction amplitude, thenthe overall behavior change will be a function of various conductionamplitudes across the pertinent nerve tracts or groupings:Φ=fΣ ^(n)(1−k·ε ²)  Equation 11where k is a constant for a given nerve environment, relating to thestrain E at which conduction amplitude approaches zero, and n is aseries of pertinent neural tracts.

Altered neuronal function (hence neurological behavior) is a function ofthe aggregate of strain, rate of strain, anatomically specificconduction decrement and time. The behavior change Φ will relate to therate of decay of conduction amplitudes.

Therefore,

$\begin{matrix}\left. {\Phi = {\left\{ {f\;{\Sigma^{n}\left( {1 - {k\; ɛ^{2}}} \right)}} \right\} \cdot {f(t)}}} \right\}^{- 1} & {{Equation}\mspace{14mu} 12} \\{\mspace{14mu}{= {{1/\left\{ {f\;{\Sigma^{n}\left\lbrack {1 - {k\left( {x/r} \right)}^{2}} \right\rbrack}} \right\}} \cdot {f(t)}}}} & {{Equation}\mspace{14mu} 13}\end{matrix}$where x is the distance between the pertinent fiber tract and theventral surface of the neuraxis. For instance, x for a fiber tract inthe midsection of the neuraxis, is equal to half of the width of theneuraxis, whereas a nerve tract on the dorsum of the neuraxis would havea magnitude equal to the thickness of the neuraxis.

And where r is the radius to the arc drawn along the ventral surface ofthe neuraxis (FIG. 37). Now k is proportional to rate of strainapplication, such that k will increase directly with rate of strain ofthe neuraxis.

The formula is based on the supposition of a relationship between theprobability of behavioral change and various factors, such as theaggregation of von Mises stress on composite nerve fibers, such as thedeformative stress of the nerve fibers of the cortical spinal tract,dorsal spinal tract, dorsal column tract, autonomic function tract, andrespiratory function tract. Without wishing to be bound by theory,neural conductivity is diminished by deformative stresses, andneurological dysfunction is related to abnormal stress inducingmodulation of the brainstem and upper spinal. Additionally, theformulation above reflects only the effects of biomechanical stress onneurological behavior, and does not assume to convey the effects of themultitude of other factors, such as, but not limited to, disorders ofembryology, metabolism and endocrinology, the effects of toxins, tumoror pharmacology, altered circulation, anatomy and trauma.

The aforementioned mathematical algorithms can be incorporated in acomputer readable software medium or medical imaging computationaldevice to determine neuraxial strain, neuraxial stress and predict theprobability of developing abnormal behavior, such as a neurologicaldisorder, in a given subject. Specifically, in a population of subjectswith pain, bulbar symptoms, myelopathy, abnormal clivo-axial angle,abnormal neuraxial angle, abnormal neuraxial strain, abnormal neuraxialstress or combinations thereof, the computer readable software mediumand/or medical imaging computational device may calculate a value, basedon images of the patient's brainstem and spinal cord, that can becompared with tables of predetermined values to provide a relativeprobability of the subject expressing abnormal behavior as a result ofthe observed neuraxial deformation. The computer readable softwaremedium and medical imaging computational device may also be used as auseful diagnostic tool for neuroradiologists to determine whether apatient's existing neurological disorder may be attributed to orexacerbated by abnormal neuraxial deformation, specifically abnormalneuraxial stress and/or strain. In an exemplary embodiment, the softwaremedium and medical imaging computational'device may be used to:accurately measure various anatomical features of a patient, and analyzethe dynamic relationships of a patient's anatomy, including: calculatingthe angle between the bone members encasing the CNS, neuraxial angle,clivo-axial angle, basal angle, and/or magnitude of neuraxial strain andstress, making a calculation as to where the physical stress due tobiomechanical deformity should be lessened to alter gene expression andnormalize cell membrane, physiology to relieve the neurological deficitand concomitant alteration of behavior, determining the probability ofwhether the patient's neurological disorder may be substantially causedby or contributed to abnormal neuraxial deformation, recommending acourse of treatment to correct the neuraxial deformation, includingspecifying the angle of correction necessary to rectify the neuraxialdeformation, providing visual displays showing the neuraxial deformationbefore and after a proposed corrective surgical procedure or anycombination thereof. A surgeon may subsequently surgically correct theneuraxial deformation based on the information and calculations providedby the computer readable software medium and medical imagingcomputational device to enable spinal stabilization and/or treat aneurological disorder. Specifically, the surgeon may stabilize thecraniospinal junction in a manner that normalizes the stresses of theCNS and returns to normal the cell membrane physiology and geneexpression. The neuraxial deformation may be corrected using the spinalstabilization systems of the present invention or any conventionalspinal stabilization device that may be used to stabilize thecraniospinal junction. In an exemplary embodiment, the neuraxialdeformation may be reduced by surgically correcting the clivo-axialangle such that is adjusted to about 145° to about 175°, more preferablyabout 150° to about 175°, and more preferably about 155° to about 175°,and most preferably, about 150° to about 170°. In another exemplaryembodiment, the neuraxial deformation may be normalized by correctingthe neuraxial angle such that it is adjusted to about 170±about 10 in aneutral position and about 165±about 10 when fully flexed.

In an exemplary embodiment, the computer readable medium and medicalimaging computational device may computationally assess the strain orstress within the brainstem using an algorithm that determines thecenter line of the medulla, calculating the neuraxial angle, promptingsurgical stabilization recommendations upon finding an abnormalneuraxial or an abnormal clivo-axial angle, computing the change instrain or stress that results from the abnormal neuraxial angle and/orabnormal clivo-axial angle, associating the strain or stress with aprobability of altered neurological function and/or behavioral change,recommend a surgical treatment means for stabilization of thecraniospinal junction. In general, the method for treating neurologicaldisorders may involve any combination of the any of the steps of any ofthe aforementioned embodiments.

In another embodiment, the invention is directed to a method fortreating a neurological disorder, preferably a neurological behavioraldisorder. The method involves determining the presence of and assessinga neuraxial deformity of a patient with an existing neurologicaldisorder, preferably a neurological behavioral disorder. Specifically,the method involves measuring and/or calculating the clivo-axial angleand/or neuraxial angle, so as to determine whether the patient has anabnormal clivo-axial angle and/or neuraxial angle. This information maybe obtained from radiographic images of the patient's occipitocervicaljunction, brainstem and/or spinal cord by measuring one or more aspectsof the patient's anatomical feature defining the clivo-axial angleand/or neuraxial angle. Exemplary measurements may include the length ofan outside perimeter, insider perimeter or midline of the brainstem andspinal cord; the width or thickness of multiple regions of the brainstemand spinal cord; and the length of medulla and upper spinal cord on theventral and dorsal surface (for the fourth ventral). These measurementsand/or calculations may be performed using a medical imagingcomputational device that supports, runs and/or is controlled by acomputer readable software for identifying, calculating and/or measuringthe neuraxial angle and/or clivo-axial angle or combinations thereof.

The method further involves determining whether the neuraxial deformitysubstantially contributes to or causes of the neurological disorder.This may be accomplished by using the medical imaging computationaldevice and software program to compare and/or mathematicallymanipulating these measurements to obtain meaningful calculationsindicative and/or determinative of the presence of abnormal stresses andstrains of the brainstem. For example, any of the aforementioned methodsfor determining neuraxial stress and/or strain, including the algorithmsand computer generated models of the patient's brainstem and spinalcord, may be used. Whether the neuraxial deformity substantiallycontributes to and/or causes the neurological disorder may similarly bedetermined from the quantified neuraxial stress and/or neuraxial strainusing any of the aforementioned methods in the present invention,including using the probability algorithms based on electro-conductivityand/or the evaluation of neuraxial stress, clivo-axial angle and/orneuraxial angle, and clinical findings such as, neck pain and/orheadache, bulbar findings, myelopathy and cranio-vertebral instability.Subsequently, the neurological disorder may be treated by correcting theneuraxial angle and/or clivo-axial angle so that it is normalized withacceptable limits using a conventional and/or spinal stabilizationsystem of the present invention.

The present invention is also directed to a method for treatingcranio-vertebral instability, a condition that results in abnormaldeformative stress of the brainstem, cranial nerves and upper spinalcord. The method may involves accessing a patient for cranio-vertebralinstability by evaluating whether the patient exhibits: (1) one or moreof the following radiographic findings: a clivo-axial angle of about135° or less, basion to odontoid displacement of about 1 cm or more;anterior displacement of the basion of about 12 mm or more from theposterior axillary line; and radiological findings used to delineatebasilar invagination, such as the odontoid rising above Wackenheim'sline, the odontoid rising above McGregor's line, the odontoid risingabove Chamberlain's line, or basilar invagination determination by theJohnell Redlund technique; (2) headache and/or neck pain; (3) two ormore of the following symptoms and/or signs of neurological dysfunctionpertaining to the brainstem and spinal cord: imbalance, vertigo,dizziness, sensory change, such as changes in vision or eye movements,respiratory dysfunction, sleep apnea, autonomic dysfunction, such aspositional orthostatic tachycardia; gastrointestinal dysfunction, suchas irritable bowl syndrome; scoliosis, genit-urinary dysfunction,syringomyelia, and other bulbar symptoms set forth in Table 2. As partof the assessment, the method involves determining the presence of anabnormal clivo-axial angle, preferably measuring or otherwisequantitatively determining the clivo-axial angle. Optionally, the methodmay involve determining the presence of an abnormal neuraxial angle,preferably quantitatively determining the neuraxial angle.

Upon accessing the presence of cranio-vertebral instability, thecranio-vertebral instability may be treated by subjecting any areas ofthe neuraxis that are compressed or deformed as a result of out of planeloading to decompression. Subsequent to decompression, thecranio-vertebral instability may be treated by stabilizing theoccipitocervical junction so as to normalize the neuraxial angle and/orclivo-axial angle. This may be accomplished by connecting a plateattached to a patient's cranium to one or more spinal rods, and/or othercomponents of a spinal stabilization system, in a manner so as toachieve a normalized neuraxial angle and/or clivo-axial angle, asdescribed in the application of the spinal stabilization system of thepresent invention. Any of the spinal stabilization systems of thepresent invention or any conventional spinal stabilization device thatmay be used to stabilize the craniospinal junction and normalize theneuraxial angle and/or clivo-axial angle.

The invention is further directed to a method for treating aneurological disorder arising from, underlying and/or associated withcranio-vertebral instability by treating the underlying cranio-vertebralinstability in the same manner as described above. For example, thismethod may be used to treat cervico-medullary syndrome which resultsfrom cranio-vertebral instability.

Without wishing to be bound by theory, it is believed that particularneurological pheotypical behavior may be related to the particularneurons involved, the overall length of time of biomechanical neuronaldeformity and the severity of deformity. Therefore, behavior phenotypeis a function of the aggregate of anatomically specific neuronaldysfunction. The assessed or measured neuraxial deformity induced stressacross the CNS may mathematically relate in a non-linear manner toalteration of gene expression and cell membrane physiology. Bycorrecting the aforementioned abnormal neuraxial strain and stress, thepresent invention may present a treatment for physical abnormalitiesresulting from changes in gene expression and altered cell membranephysiology, resulting in changes in neurological function andconcomitant changes in behavior. Additionally, the stresses alteringgene expression and membrane physiology may be maintained at a morenormal level of functioning by the immobilization of the boneencasements around the CNS in a normal or close to normal relationship.By decreasing neuraxial deformity induced stresses in the CNS, it may bepossible to favorably alter neuronal gene expression and cell membranephysiology with the result that neurological function at the level ofthe brainstem and upper spinal cord may improve.

EXAMPLES Example 1

In a clinical study, neuraxial deformative stress was corrected toaddress cervico-medullary syndrome resulting from the dynamicdeformation of the cranio-cervical junction and spine in patientsdiagnosed with Ehlers-Danlos Syndrome. The study suggests thatcorrection of neuraxial stress may be an effective treatment forneurological deficits arising from deformative stresses of the brainstemand upper spinal cord in Ehlers-Danlos Syndrome (EDS) patients.Additionally, the study suggests that correction of neuraxial stress maybe an effective treatment for Ehlers-Danlos Syndrome (EDS) or anunderlying neurological disorder thereof.

Open intraoperative decompression and fusion of the craniocervicaljunction was performed on 55 patients diagnosed with EDS who hadabnormal clivo-axial angles of about 135° or less. The cranio-cervicalangle of these patients was improved on average by about 25° andcorrected to about 150° to about 165° during fusion of the surgicalprocedure. In general, ligamentous instability in EDS causescranio-vertebral instability, kyphosis of the clivo-axial angle anddeformation of the brainstem and cord. Additionally, neuraxialdeformative stress arising from EDS causes cervico-medullary syndrome,which is characterized by headaches, neck pain, bulbar symptoms andmyelopathy.

One year after the surgical procedure, random groups of the patientswere asked to evaluate whether they noticed a change in theirneurological function, pain and quality of life. The patients were alsoasked whether they returned to work or school, whether, looking back,they would still have consented to the surgery in view of theirexperience, whether they would recommended the surgery to a friend orfamily member and whether they experienced any complications.

Based on the follow-up clinical examinations and patient responses, itwas determined that reduction of neuraxial deformative stress bynormalization of clivo-axial angle and cranio-cervical stabilizationdecreased pain, improved patient function, enhanced quality of life anddecreased neurological deficits. Specifically, in a first group of 12randomly sampled patients, all the patients reported that, looking back,they would still have consent to the surgery based on their experienceand would recommended the procedure to a friend or family member. Ofthis group, 12 patients reported an improved neurological change. 10patients reported an improved functional change, and 2 patients reportedno functional change. 11 patients reported an improved quality of life,and 1 patient reported no change in quality of life. 11 patientsreported a decrease in pain, and 1 patient reported no change in pain.Additionally, of the 12 patients, 8 were able to return to work orschool, 2 expected to return to work/school soon and 1 was retired. Only1 patient did not expect to return to work/school.

In a second group of 6 randomly sampled patients, all the patientsreported that, looking back, they would still have consent to thesurgery based on their experience and would recommended the procedure toa friend or family member. Of this group, 6 patients reported animproved neurological change. 4 patients reported an improved functionalchange while 2 patients reported a worsened functionality. 6 patientsreported an improved quality of life. 6 patients reported a decrease inpain, and 1 patient reported no change in pain. 5 of the patients wereable to return to work or school, and 1 patient expected to return towork/school soon.

In a third group of 11 randomly sampled patients, all the patientsexcept for one reported that, looking back, they would still haveconsent to the surgery based on their experience. Furthermore, all thepatients indicated that they would recommend the procedure to a friendor family member. Of this group, 10 patients reported an improvedneurological change and 1 patient reported a worsened neurologicalstate. 9 patients reported an improved functional change while 1 patientreported no change in functionality and 1 patient reported a worsenedfunctionality. 9 patients reported an improved quality of life while 1patient reported no change in quality of life and 1 patient reported aworsened quality of life. 10 patients reported a decrease in pain, and 1reported worsened pain. 5 of the patients were able to return to work orschool, and 3 patients expected to return to work/school soon. Only 3patients did not expect to return to work/school.

Example 2

In a clinical study, circumstantial and statistical evidence suggestedthat autism spectrum disorder (ASD) and cervico-medullary syndromes arelinked. As part of the study, children diagnosed with cervico-medullarysyndrome were found to have statistically significant improvement inevery metric except ASIA scores and SF-36 mental component as a resultof suboccipital decompression for Chiari malformation and reduction,fusion-stabilization for ventral brain stem compression or basilarinvagination. For the subset of patients with ASD suffering fromcervico-medullary syndromes, surgery to correct the anatomical deformityyielded marked improvement in a number of clinical metrics for accessingfunctionality, suggesting that the surgical procedure may be aneffective treatment for ASD or an underlying neurological disorderthereof.

Method

The study involved the reduction of deformative stresses in thecraniocervical junction of ten children with Chiari malformation andvarious forms of basilar invagination. Four of the ten children fromthis group had been diagnosed with ASD, a higher than expected rate ofoccurrence of ASD in a sample population. By Bayes' Theorem, this wouldimply that there is a higher than expected rate of cervico-medullarysyndromes in the population of patients with ASD.

Three of the four subjects were evaluated prospectively and oneretrospectively, pre-operatively and post-operatively at 1, 3, 6, andevery 12 months for quality of life (SF-36), American Spinal InjuryAssociation Impairment scale (ASIA), pain (Visual Analog Scale, VAS),Oswestry Neck Disability Index, function (Karnofsky Index) andassessment of bulbar symptoms (the Brainstem Disability Index—twentyquestions relating to bulbar symptoms in Table 2). To maximizeobjectivity, all data, with the exception of the ASIA scale, werecollected independently by a research assistant while the surgeon wasnot present.

Surgical Criteria

All subjects in the study were referred by a pediatric neurologist withpain, disability, neurological deficits and radiological findings thatidentified a surgically treatable disorder. Each of these 4 patients hadbeen previously diagnosed with ASD, which may include a diagnosis ofprobable autism, based upon significant social, verbal and motor skilldelay, with mild cerebral palsy and disordered sensory integration.

Subjects met the following surgical criteria: i) moderate to severeheadache or suboccipital pain; ii) evidence of myelopathy; iii) presenceof bulbar symptoms and iv) at least one of the following radiologicalcriteria: Chiari Malformation Type I, basilar invagination byconventional or “non traditional criteria” or functional cranialsettling with abnormal clivo-axial angle. A listing of behavioraldiagnoses, radiographic diagnoses, neurological signs and symptoms ispresented in Table 1. Bulbar symptoms that were considered are listed inthe Table 2.

TABLE 1 Patient Characteristics Age Behavioral Pre/Post-Op F/up Patient# (yrs) Diagnosis Radiographic Diagnosis CVA* B-pC2** OutcomeComplications (mos) 41 8 Atypical Medullary kyphosis, 132°/180° 9 mm +++∅ 17 autism functional cranial settling, hypermobility 36 15 Asberger'sAbnormal clivo-axial 135°/170° 9 mm +++ ∅ 13 Syndrome angle, Chiari 0Malformation 34 5 Autism Chiari I Malformation with 134°/165° +++ ∅ 36ventral brainstem compression 40 5 Autism Chiari I Malformation150°/150° ++ ∅ 20 CVA* = preoperative and postoperative Clivo-axialangle B-pC2** = Grabb-Oakes measurement of ventral brainstemcompression, basion to ventral inferior C2

TABLE 2 The following 20 symptoms may be referable to pathology at thelevel of the brainstem.   Double vision Memory loss Dizziness VertigoRinging in the ears Speech difficulties Difficulty swallowing Sleepapnea Snoring or frequent awakening Choking on food Hands turn blue incold weather Numbness in your arms and shoulders Numbness in your backand legs Get tired very easily Unsteady walking More clumsy than youused to be Urinate more often (every 1-2 hours) Irritable bowel diseaseor gastro esophageal reflux disease Weaker than you would expect in yourarms or hand Weaker in your legsSurgical Procedure

The surgical intent was to reduce deformative stress of the brainstem bydecompressing the Chiari malformation and reducing the angulation of thebrainstem around the odontoid. The surgical procedure involved removingthe foramen magnum posteriorly in the cases of Chiari malformation(subjects #2, 3, 4) alteration and normalization of craniocervicalrelationships, and the stabilization and fusion of the correctedrelationship (subjects #1, 2, 3). Subject #4 suffered from Chiarimalformation without evidence of ventral brainstem compression. Hesolely underwent craniocervical decompression to address Chiarimalformation.

Surgical stabilization of the occipitocervical junction was performedwhile the patient positioned prone in a Mayfield headholder. Sensory andmotor evoked potentials were monitored throughout the procedure. Onlythe subocciput and upper two or three vertebrae were exposed, and asuboccipital craniotomy was performed to the extent necessary todecompress the Chiari malformation where present.

A titanium plate (Altius™, Biomet, Parsippany, N.J.) was contoured tothe occiput, and fastened to the skull with screws appropriate to thebone thickness as determined by preoperative CT scans. After exposure,intra-operative reduction of the craniocervical junction was performedunder real-time fluoroscopy, evoked potential monitoring and directvisual inspection: the cranium was placed in traction, posteriorlytranslated and then extended the craniocervical junction to reduce theclivo-axial angle and to basilar invagination, restoring the basion toits normal context above the odontoid process. Fluoroscopy was used toconfirm a normalization of the clivo-axial angle to about 150° to about165°.

The craniospinal stabilization utilized screws placed in the C1 lateralmass, and in the C2 pedicles, and when additional purchase wasnecessary, in the C3 lateral masses. The bone surfaces weredecorticated; segments of two ribs were harvested, contoured to thesuboccipital bone and upper cervical vertebrae and augmented withdemineralised bone matrix. Both wounds were then closed over drains. Thepatients were mobilized usually one day after surgery in a neck brace(Miami J™, or equivalent) for 6 weeks. The brace was removed after 6weeks and gentle range of motion exercises initiated.

Results

The results of the study are summarized in Tables 3-9. Postoperatively,all but 3 bulbar symptoms (weakness in legs, fatigue, and memory loss)were eliminated completely from this cohort of patients (See Table 3).No new bulbar symptoms appeared as a result of surgery. Incidence ofbulbar symptoms was reduced from a preoperative mean of 11.5 per patientto a postoperative mean of 1 per patient (See Table 4).

TABLE 3 BEFORE SURGERY AFTER SURGERY (0 MONTHS) (12 MONTHS) SYMPTOMSNUMBER PERCENT NUMBER PERCENT Double Vision 2 50 0 0 Memory Loss 3 75 125 Dizziness 1 25 0 0 Vertigo 2 50 0 0 Ringing in the Ears 1 25 0 0Difficulty Swallowing 2 50 0 0 Sleep apnea 3 75 0 0 Snoring 3 75 0 0Choking on food 1 25 0 0 Hands Turn Blue in 0 0 0 0 Cold WeatherNumbness in arms and 3 75 0 0 shoulders Numbness in back 3 75 0 0 andlegs Get tired easily 4 100 2 50 Unsteady walking 3 75 0 0 Clumsiness 375 0 0 Urinary frequency 3 75 0 0 Irritable bowel or GERD 2 50 0 0Sexual Difficulty 1 25 0 0 Weakness in arms 3 75 0 0 and hands Weaknessin legs 3 75 1 25

TABLE 4 Table - Bulbar Symptoms BII (0 months) BII (12 months) G41 55 5G36 40 0 G34 55 0 G40 80 15

Preoperative pain scores according to the Visual Analog Scale averaged27.5/100. At the 12-month follow-up, not a single patient reported pain,for a mean score of 0/100 (See Table 5). Karnofsky scores improved inevery patient, with a pre-operative mean of 65 and a postoperative meanof 90 (See Table 6). Oswestry Neck Disability Index scores improved inall patients, from a pre-operative mean of 46.7 to a post-operative meanof 10.5. One patient did not complete the Oswestry NDI preoperatively(See Table 7).

TABLE 5 PAIN/Visual Analog Scale Pt. # Pain (Pre-Op) Pain (12 MonthsPost-Op) 41 10/100 0/100 36 40/100 0/100 34 40/100 0/100 40 20/100 0/100

TABLE 6 Table - Karnofskv Index Pt. # KPS (0 months) KPS (12 months) G4150 70 G36 80 100 G34 50 100 G40 80 90

TABLE 7 Table - Oswestry Neck Disability Index Pt. # Neck (0 months)Neck (12 months) G41 46 4 G36 32 12 G34 N/A 10 G40 62 16

SF-36 Quality of Life Survey norm-based scores improved in every patientin the physical component. The mental component was more variable.Preoperative physical/mental means were 40.8/45.9 (See Table 8).Postoperative means were 58.2/53.1 (See Table 8). There was nosignificant change in ASIA scores, which were only collected on 3 out of4 patients. Only one of these showed an ASIA score below perfectpreoperatively. All ASIA scores were normalized postoperatively (Table9).

TABLE 8 SF-36 Quality of Life (norm-based) SF-36 Physical SF-36 PhysicalSF-36 Mental SF-36 Mental Patient (0 months) (12 months) (0 months) (12months) G41 34.9 55.1 64.5 57.8 G36 42 59.4 54 48.3 G34 33.5 60.1 21.858.7 G40 52.9 58 43.4 47.4

TABLE 9 ASIA ASIA ASIA Patient # (0 months) (12 months) G41 304 324 G36324 324 G34 N/A N/A G40 324 324

No behavioral metrics were used pre- or post-operatively. However, thesubjective opinion of the parents of all 4 subjects was consistent withincreased socialization and verbal skill.

Discussion

Despite the presence of ASD, the subjects appeared to benefit fromsurgical treatment. There was a statistically significant improvement interms of pain, quality of life, function and number of bulbar findings.Furthermore, 100% of parents reported improvement in socialization andverbal skills.

There appeared to be a high co-incidence of ASD and cervico-medullarysyndromes exists based on: the results of 3 recent surveys indicating anASD prevalence rate in the United States of approximately 60 per 10,000,suggesting that approximately 1/166 individuals in the community haveASD. Thus, if the conditions are independent it would be unlikely tofind one or more cases of ASD in small sample populations. In thepresent study concerning cervico-medullary syndromes, 4 of the 10children participating in the study had been previously diagnosed withASD. If the conditions were truly independent, this would be a highlyunlikely finding. A two-tailed binomial test for independence (used dueto small sample size) gave strong significance with p=2.7×10⁻⁷,suggesting that the probability of such an observation arising purelydue to chance is miniscule if the conditions are independent. Thisevidence supports the possible co-incidence of ASD and cervico-medullarysyndromes.

Bayes' Theorem states that if P(A) is the probability of A occurring andP(A|B) is the probability of A occurring given B occurring then:P(A|B)=P(B|A)*P(A)/P(B) (Bayes 1763). Thus if P(B|A) is greater thanP(B), then P(A|B) is greater than P(A). In the context of this study, alarger than expected number of patients with cervico-medullary syndromessuffering from ASD would imply that a larger than expected number ofpatients suffering from ASD have cervico-medullary syndromes, perhapsundiagnosed.

Conclusion

For the subset of patients suffering from ASD and cervico-medullarysyndromes, surgical intervention that remedies the underlyingphysiological abnormality can significantly improve pain, function andquality of life. There is both circumstantial and statistical evidencesuggesting a heightened incidence of ASD diagnosis among childrensuffering from cervico-medullary syndromes, and consequently aheightened incidence of cervico-medullary syndromes among childrendiagnosed with ASD. In view of the improved behavioral functionalityexhibited by the children ASD and cervico-medullary syndromes, thepresent study suggests that surgical procedures reducing deformativestress may be effective for treating ASD or an underlying neurologicaldisorder thereof.

Example 3

In this study, a cohort of ten subjects having symptomaticcervico-medullary syndrome were surgically treated by normalization ofthe clivo-axial angle and craniocervical fusion and stabilization forcorrection of deformity. The study demonstrates the importance ofreducing deformative stress in the etiology of neurological signs andsymptoms associated with craniocervical disorders.

Surgical Criteria

The subjects were admitted to the protocol if they met the followingsurgical criteria: i) moderate to severe headache or suboccipital pain;ii) evidence of brainstem encaphelopathy; iii) evidence of myelopathy;and iv) basilar invagination or Chiari malformation, and v) aclivo-axial angle less than 135°. Bulbar symptoms that were consideredare listed in Table 2. Presenting symptoms are listed in Table 10.

TABLE 10 Patients and Symptoms Patient ID Age Sex Presenting SymptomsPostoperative Symptoms G20 37 F Extremity numbness, weakness Resolutionof all symptoms, some in arms (right) and legs, painful numbness in handand feet remained, prickling from hands to scalp, no weakness blurredvision, loss of coordination, headaches, low- back pain, chronic fatigueG13 33 F History of syringomyelia, Resolution of all symptoms headaches,siezure-like episodes, nystagmus, increased motor tone G17 44 MHeadaches, memory loss, pain, Resolution of headaches, pain, vertigo,gagging, vertigo, progressive blurred vision and sensory loss, weakness,sensory loss, blurred vision, increasing bowel and urinary dificukies G855 F History of rheumatoid arthritis, Resolution of all symptoms neckpain, paraesthesias is hands exacerbated by lateral rotation, fatigue,urinary frequency, clumsiness, weakness in arms and hands G14 58 MUrinary frequency, incontinence, Resolution of all symptoms sexualdifficulties, numbness, weakness, clumsiness, fatigue, memorydifficulties, ringing in ears, neck stiffness, quadriparesis G2 80 FInflammory lesion around deltoid All symptoms resolved, some difficultyligament, neck stiffness and pain, swallowing left patellar tendonhyperreflexia, left-sided dysdiadochokinesia G7 65 F History ofKlippel-Feil Syndrome Normal strength and sensation, some and bipolardisorder, neck pain, hypaesthesia at C5, pain reduced but patchy sensoryloss, absent gag not absent reflex, balance and urinary difficulties G337 M Progressive neck pain Occasional dizziness with rapid head turningG9 65 M Fatigue and numbness in left arm All symptoms resolved, someleft-sided and leg, visual changes, dysdiadochokinesia dizziness,vertigo, GED, headaches, urinary frequency G6 63 M Sleep apnea,spasticity, Normal strength and sensation, weakness, some sensory loss,neuralgia paraesthetica on left side, neck pain, urinary difficultiesresolution of all brainstem symptomsSurgical Procedure

The goal of surgery was to reduce deformative stress of the brainstem byreducing the angulation of the brainstem around the odontoid (making theclivo-axial angle more obtuse). The surgical procedure involvedalteration and normalization of craniocervical relationships, and thestabilization and fusion of the corrected relationship utilizing 2autologous rib grafts for the fusion.

The subjects of this cohort were referred for bulbar findings,myelopathy and pain referable to brainstem and upper spinal cordcompression, and neuroradiological findings of non-traditional forms ofbasilar invagination, or ventral brainstem compression. The relativelyhorizontal clivus and corresponding craniocervical kyphosis in thesesubjects required normalization of the clivo-axial angle and fixation ofthe skull in a more vertical position.

Clinical Metrics

Subjects were evaluated pre-operatively and post-operatively at 1, 3, 6,and every 12 months for quality of life (SF-36), American Spinal InjuryAssociation Impairment scale (ASIA), pain (Visual Analog Scale, VAS),Oswestry Neck Disability Index, function (Karnofsky Index) andassessment of bulbar symptoms (the Brainstem Disability Index—twentyquestions relating to bulbar symptoms in Table 2). To maximizeobjectivity, all data, with the exception of the ASIA scale, werecollected independently by the research assistant while the surgeon wasnot present. Measurement of clivo-axial angle and determination ofdegree of ventral brainstem compression was conducted independently by aneuroradiologist.

Results

Clivo-Axial Angle

Clivo-axial angles were normalized from a mean of 135.8° preoperatively(range 131°-140°) to 163.7° measured at the 12-month follow-up (range150°-176°) in the neutral position. For consistency, measurements referto angulation in the neutral position.

Neurological Signs and Symptoms

Presenting and post-operative symptoms are listed in Table 10. Commonsymptoms included sensory changes (hypoesthesias or paresthesias),headache or neck pain, memory loss, clumsiness with frequent falls,uncertain gait, fatigue, and weakness in the upper or lower extremities.Subjects often reported gastroesophageal symptoms, respiratorydisturbances, vestibular, auditory, or visual disturbance, and bowel orbladder dysfunction.

Every subject reported substantial improvement in most symptoms withinthe first postoperative month. In most subjects, improvement continuedover the entire length of the follow-up period (See Table 10).

Clinical Metrics

A summary of clinical data is presented in Table 11. Metrics werecompared between preoperative measurement and measurement at the12-month follow-up. Formed SF-36 physical component scores increasedfrom a mean of 38.09 to a mean of 50.98. Mental component scoresimproved from a mean of 45.68 to a mean of 56.31. Mean Karnofsky scoreincreased from 80 to 97. Mean pain as measured by the Visual AnalogueScale decreased from 5.6 to 1.1. Oswestry Neck Disability Index scoresdecreased from a mean of 38.75 to a mean of 10.89. Mean ASIA scoreimproved from 296.4 to 314.8. The mean number of bulbar symptoms perpatient decreased from 10.3 symptoms per patient (out of 20) to 2.26symptoms per patient.

TABLE 11 Mean Clinical Metrics Pre- 12-Month P-value P-value fromoperative Followup from non-parametric Mean Mean T-test test SF-36Physical 38.09 50.98 0.001 0.010 Component SF-36 Mental 45.68 56.310.008 0.006 Component Karnofsky Scale 80 97 0.0003 0.008 Visual-Analog5.6 1.1 0.001 0.007 Pain Scale Oswestry Neck 38.75 10.89 0.006 0.016Disability Index ASIA Scale 296.4 314.8 0.004 0.014 Number of 10.3 2.260.002 0.009 Bulbar Symptoms Clivo-Axial Angle 135.8 163.7 <10⁻⁵ 0.01

Improvement reached statistical significance with each metric: ASIA(p=0.004), Oswestry Index (p=0.006), Karnofsky Index(p=0.0003), VAS(p=0.0009), number of bulbar symptoms (p=0.002), SF-36 physicalcomponent (p=0.001) and SF-36 mental component (p=0.008). Non-parametricWilcoxon signed-rank tests were statistically significant (p<0.02 forall tests).

The number of patients answering ‘yes’ to each question in the list ofbulbar symptoms pre-operatively and at the 12-month follow-up is listedin Table 12.

TABLE 12 Bulbar Symptoms Before and After Surry Number of Number ofPatients Affected Patients Affected at 12-Month Symptom Before SurgeryFollowup Double Vision 5 0 Dizziness 6 1 Vertigo 3 0 Ringing in the Ears6 3 Difficulty Swallowing 3 1 Sleep apnea 5 0 Snoring 6 4 Memory Loss 51 Choking on food 2 1 Hands Turn Blue in Cold Weather 3 0 Numbness inarms and shoulders 6 1 Numbness in back and legs 4 2 Get tired easily 82 Unsteady walking 7 1 Clumsiness 9 0 Urinary frequency 7 2 Irritablebowel or GERD 4 1 Sexual Difficulty 3 1 Weakness in arms and hands 8 0Weakness in legs 3 2Discussion

An abnormally acute clivo-axial angle causes lengthening of the medullaand spinal cord. The study determined that with sufficient deformativestress, patients will experience pain, neurological deficit and loss ofquality of life and that correction of the clivo-axial angle decreasesthe neuraxial deformative stress, thereby significantly improving pain,neurological deficit, function and quality of life.

Clinical Outcomes

The statistically significant improvements in VAS, ASIA scale, KarnofskyIndex, SF 36 (both physical and mental) and the Bulbar Systems Indexsupport the notion that normalizing the clivo-axial angle results inclinical improvement. metrics used are widely validated. Absent gagreflex, vocal cord dysfunction, and facial sensory loss of pinprick wereamong the most common findings. Respiratory and gastrointestinaldisorders were highly represented in this series, as in others whereapnea was attributed to brainstem deformity. The clinical outcomes areconsonant with those of others.

Platybasia

Platybasia is defined by the basal angle, formed by a line extendingacross the anterior fossa from the nation to the tip of the dorsumsella, and a second connecting line drawn along the posterior margin ofthe clivus. In normal adults, the basal angle is about 116°±about 6°,and in children about 114±about 5°. As the basal angle increases(becomes more flattened), the clivo-axial angle becomes morepathological.

Platybasia per se has no intrinsic clinical significance, but is oftenassociated with encephalomyelopathy from an abnormal clivo-axial angleand medullary kink, such as seen in Ehlers Danlos Syndrome,achondroplasia, osteogenesis imperfecta, Paget's disease.

Complications

No major complications were observed in this cohort. However,postoperative CT in two subjects showed pedicle screws adjacent to thevertebral artery within the vertebral foramen at C2 as described byothers. At the C1 level, the lateral mass screw, if not aimed medially,has a 84% probability of emerging near the ICA on at least one side, anda 47% probability of doing so on both sides.

A concern is the limitation of neck rotation after craniospinal fusion.Fifty percent of neck rotation occurs between C1 and C2, and there isnormally approximately 21° of flexion between the occiput and cervicalspine; however, most subjects in this series report some degree ofnormalization of neck movement at one year. This is due to compensationat lower cervical levels, compensatory torso rotation and remodeling ofvertebrae.

Pathophysiology

The observed recoverability in these injuries is consistent with theobservation in experimental models that axons subjected to strainrecover rapidly, both anatomically and functionally.

The spinal cord elongates with flexion of the neck. At a strain ε=0.2the giant squid axon is rendered non-conductive, and the murine opticnerve histologically manifests axon retraction-balls. Stretching of theaxolemma may result in several levels of injury: electron micrographsshow clumping, loss of microtubules and neurofilaments, loss of axontransport and accumulations of axoplasmic material identified as theretraction ball, analogous to diffuse axonal injury (DAI) in the brainand seen in basilar invagination, and “Shaken Baby Syndrome”. Stretchedneurons undergo up-regulation of N-Methy D-Aspartate receptors, whichcauses heightened vulnerability to peroxynitrites and reactive oxygenspecies, and concomitant mitochondrial dysfunction and DNAfragmentation, or apoptosis of neurons and oligodendrocytes.

The strain due to stretching of the neuraxis is greatly increased bycompression, or “Out-of-plane” deformative stress due to herniatedcerebellar tonsils, pannus over the odontoid, or retroflexed odontoid.

Conclusions

This study supports the determination that abnormal bending of theneuraxis over the “fulcrum of the clivus-atlas-odontoid complex” causesneurological dysfunction, and that in these subjects, open-reduction ofcraniospinal deformity (normalization of the clivo-axial angle),stabilization and fusion is efficacious in improving pain, quality oflife, neurological deficit, function and relief of bulbar symptoms. Inthis study, we have focused upon normalization of the clivoaxial anglewith the specific intent of mitigating the deformative stresses thatarise in the setting of deformation of the upper spinal cord and medullaoblongata due to abnormal clivo-axial angle.

Example 4

In a clinical study, it was determined that, in some circumstances,Chiari malformation, functional cranial settling and subtle forms ofbasilar invagination result in deformative neuraxial stress, manifestedby bulbar symptoms, myelopathy and headache or neck pain. Using finiteelement analysis (FEA) as a means of predicting stress due to load, alinkage between FEA-predicted deformative neuraxial stress and metricsof neurological function was established. When abnormal neuraxial stresswas corrected, the patients showed clinical improvement corresponding tothe reduction in predicted deformative neuraxial stress within thecorticospinal tract, dorsal columns and nucleus solitarius. Paired ttests/Wilcoxon signed-rank tests comparing preoperative andpostoperative status were statistically significant for pain, bulbarsymptoms, quality of life, function but not sensorimotor status.

Method and Materials

In the study, 5 children with encephalomyelopathy due to medullarykinking, basilar invagination or Chiari malformation were evaluated by apediatric neurologist and referred for subsequent neurosurgicalevaluation. Standardized outcome metrics were used during theexaminations. Patients underwent suboccipital decompression whereindicated, open reduction of the abnormal clivo-axial angle or basilarinvagination to correct ventral brainstem deformity, andstabilization/fusion. FEA predictions of neuraxial preoperative andpostoperative stress were correlated with clinical metrics. The studywas IRB approved for neurological assessment, evaluation of quality oflife (SF-36), American Spinal Injury Association (ASIA) impairmentscale, pain (Visual Analog Scale [VAS], Oswestry Neck Disability Index),function (Karnofsky Index) and assessment of bulbar symptoms (theBrainstem Disability Index—20 questions relating to bulbar symptoms,shown in Table 2), and computational brainstem and spinal cord stressinjury analysis (SCOSIA©, Computational Biodynamics, LLC, Va Beach,Va.).

Rationale for Surgery

The following surgical criteria were used in the deliberation as towhether subjects were candidates for surgery: first, signs of cervicalmyelopathy (sensorimotor findings, hyper-reflexia); second, bulbarsymptoms (lower cranial nerve dysfunction, respiratory disorder, changesin vision or tracking, auditory vestibular symptoms, dysautonomia);third, severe headache and/or neck pain that was improved by the use ofa neck brace; and fourth, the radiographic finding of brainstemdeformation due to Chiari malformation, basilar invagination and/orventral brainstem compression, as determined by the Grabb-Oakescriterion and by the presence of abnormal clivo-axial angulation(<135°).

Each of the 5 patients studied were placed in a neck brace for at least2 weeks prior to surgery to determine whether immobilization improvedtheir clinical presentation; all showed significant improvement ofclinical symptoms while in the brace. The response to the neck bracerepresented a subjective indicator that immobilization in a neutral orslightly extended position lessened their headaches and/or neck pain.

Surgical Procedure

During surgery, each patient was positioned prone in a Mayfieldhead-holder with extension at the cervicothoracic junction and gentleflexion at the craniocervical junction to facilitate both subperiostealexposure of the subocciput and upper two or three vertebrae andplacement of the suboccipital plate. Sensory and motor evoked potentialswere monitored throughout. A suboccipital craniotomy was performed tothe extent necessary to decompress the Chiari malformations, but withcare to leave available bone surface area for the subsequent fusion. Asuboccipital plate (Altius™, Biomet, Parsippany, N.J.) was contoured tothe occiput and fastened to the skull with screw lengths appropriate tothe bone thickness as determined by preoperative CT scan. At the midline(the “keel”), the skull thickness was approximately 10 mm. Laterally,the mantle is thinner, usually accommodating a 6-mm screw.

The surgeon considered but did not perform occipito-ganglia neurectomiesbecause there were no cases of severe basilar invagination.

Open intraoperative reduction of the craniocervical junction deformitywas performed under fluoroscopy, evoked potential monitoring and directvisual inspection. Traction was utilized to the extent necessary toachieve reduction of basilar invagination. To accomplish this, thesurgeon broke from scrub, and taking hold of the Mayfield head-holderfrom the head of the table, performed a three-part maneuver: first, thecranium was placed in approximately 15 lb of traction; second, aposterior translational force was applied to bring the Basion more inline with the odontoid; third, the cranium was extended at thecraniocervical junction to reduce the clivo-axial angle, therebyrestoring the clivus to a normal relationship with the odontoid processand eliminating the medullary kyphosis. Severe basilar invagination mayrequire preoperative traction reduction or more forceful tractionintraoperatively. After normalization of the clivo-vertebralrelationship, the Mayfield head-holder was re-tightened. Fluoroscopy wasperformed to confirm an increase (normalization) in the clivo-axialangle of 20°. In the present study, a clivo-axial angle of over about160° was achieved. In most cases, the reduction technique was repeatedto maximize normalization of the clivo-axial angle. The technique ofrepeated reduction to gain further improvement of the clivo-axial angletakes advantage of the viscoelastic properties of the ligamentousstructures that stabilize the craniovertebral junction and uppercervical spine.

Craniospinal stabilization was completed utilizing screws placed in theC1 lateral mass and in the C2 pedicles. Caution was exercised duringscrew placement because the vertebral artery foramen lies medially in30% of cases, and may fall within the standard trajectory of the C1lateral mass screw. In these cases, a single screw may be placed. Whenadditional screw purchase was deemed necessary, the C3 lateral masseswere added as points of fixation. Subjects with Ehlers-Danlos syndromewho manifest significant joint laxity should have C3 lateral mass screwsincluded in the construct. The bone surfaces were decorticated; segmentsof two ribs were harvested, contoured to the suboccipital bone and uppercervical vertebrae, and augmented with demineralized bone matrix. Bothwounds were then closed over drains. The patients were mobilized in aneck brace (Miami J™ or equivalent) for 6 weeks.

Finite Element Analysis

FEA, a mathematical method that reduces a continuous structure intodiscrete finite brick elements, was used to compute estimates ofpreoperative and postoperative mechanical stress within the brainstemand spinal cord. This method allowed for the approximation of partialdifferential equations with a linear system of ordinary differentialequations, which can then be solved by numerical methods with theappropriate boundary conditions. In this particular case, the equationsconcerned mechanical strain, out-of-plane loading and materialproperties such as Young's modulus of elasticity or Poisson's ratio. TheFEA determined preoperative and postoperative mechanical stress withinthe brainstem and spinal cord compared with clinical metrics.

A FEA program (PRIMEGen) was adapted for the purpose of modeling thebrainstem and cervical and upper thoracic spinal cord under dynamicloading and strain. The resulting Spinal Cord Stress Injury Analysis(SCOSIA©) technology was also used to computes probable magnitude andlocation of stress within the brainstem and upper spinal cord.

A model of the brainstem and spinal cord that incorporatespatient-specific anatomical data, such as deformity over the odontoidprocess, lengthening of brainstem and spinal cord with flexion, andnumerous other features such as compression of the spinal cord by aherniated disc or spur, was developed to parametrically generatespecific FEA models for each patient. The computations derived fromthese models undergoing flexion and extension generated estimates of thestresses existing within the brainstem and spinal cord in the neutral,flexion and extension conditions. The estimated stresses reflect thedynamic change in stress exerted on the neural tissue. Specifically, theFEA models were used to determine the neuraxial stress for each specificpatient. Correlation of computed mechanical stresses with clinicaloutcome indices suggested a direct relationship between reduction ofdeformative neuraxial stress and clinical improvement.

Computer-driven stress analysis—based finite element formulationsprovided a unique perspective on the biomechanical behavior of the humancervical spine under normal, degenerative and iatrogenically surgicallyaltered conditions. Due to the reproducibility and repeatability offinite element models, detailed parametric analysis with regards to thegeometrical conditions and material property changes could be performed,and biomechanical responses were evaluated using FEA.

Due to the displacement-based formulation of structural finite elements,nodal displacements are primary output variables and nodal stresses arecomputed variables using nodal displacements. In other words, stressesare predicted based upon the deformation or stretching of specificnodes, with specific Cartesian coordinates within the system.

The SCOSIA system utilizes a simplified model of the brainstem andspinal cord, assuming isotropy for gray matter tracts and for the whitematter tracts, constant material properties regardless of stress,boundary conditions at the pons and mid thorax, and Young's modulus ofelasticity for bovine gray and white matter. Upright MRIs and surfacecoils would have been preferable but were not available during thisstudy; instead, cervical spine MRI in the neutral position was used todetermine “out-of-plane” loading such as arises from deformity,retroflexed odontoid, discs and spurs. Dynamic flexion/extension x-rayswere performed in the upright position to model strain due to change inlength, and for the generation of the “centroids,” the x, y, zcoordinates of the center of every level of the spinal cord, which gointo the modeling process.

The Grabb-Oakes measurement was used to determine degree of focalcompression due to VBSC. On MRI, a line was drawn from the Basion to thetip of the posterior inferior C2 vertebra. A perpendicular was drawnfrom the B-pC2 line to the dura as shown in FIG. 40. A measurement (Δ)of greater than 9 mm reflected some degree of VBSC thus in our boundaryconditions: VBSC=Δ−9, in mm.

The acquired images were transferred to the dedicated processingworkstation via DICOM; for each anatomical level, anatomical coordinateswere manually specified to assemble the model of the spine. Followinggeneration of the model, boundary conditions were imposed by fixing themodel at the T6 level, displacing it into the flexed position that thepatient's spinal cord assumed as determined by flexion x-rays, andadding out-of-plane loading to the medulla equivalent to the VBSC numberdescribed above. The analysis yielded the overall Von Mises stress foreach voxel within the model: σ=3J₂, where J₂ is the second deviatoricstress invariant. For purposes of this study, only the maximal Von Misesstress (aggregate of strain and out-of-plane loading) for each componentwas selected. Stresses representing motor skills were taken fromcomputed stresses within the corticospinal tract, sensation from thedorsal columns, and respiratory function from the nucleus solitarius anddorsal motor nucleus.

Imaging

Based on MRI images, two patients had a Chiari malformation; 1, basilarinvagination; 1, retroflexion of the odontoid; and 1, functional cranialsettling. All 5 patients were observed to have ventral brainstemcompression by the Grabb-Oakes criteria, an abnormal clivo-axial angle,abnormal neuraxial stress, and kinking of the medulla. Spinalabnormalities included assimilation of the atlas, atlanto-axialsubluxation, Klippel-Feil malformation, scoliosis and kyphosis.

Bulbar Symptoms Index

Bulbar symptoms were indexed as another metric reflecting bulbarpathology. The authors included a numerical representation of bulbarsymptoms (20 symptoms, 5% each for a total score of 100%; 0% reflectingno bulbar pathology; 100%, 20 bulbar symptoms). The symptom of decreasedmemory was included as a bulbar symptom because many of the patientshave reported the onset of memory difficulties with the other symptoms,and because there is support in the literature that memory is affectedwith alterations of the brainstem reticular activating system, sleepabnormalities, altered visual tracking or modulation of audition, andchronic pain.

Statistical Analysis

Analyses were performed preoperatively and at the last follow-uppostoperatively. Due to small sample size, both parametric (paired ttests) and nonparametric (Wilcoxon signed-rank tests) statistical testswere used for SF-36 physical component summary (PCS) scores and mentalcomponent summary (MCS) scores, VAS pain scores, summed ASIA scores,Karnofsky Index, Bulbar Symptoms Index, and SCOSIA-derived stressvalues. Pearson's correlation coefficient (r_(p)) was used to determinethe extent to which SCOSIA-derived stress values were correlatedpreoperatively and postoperatively with VAS, brainstem disabilityindices, Karnofsky values and SF-36 scores. Statistical significance wasset at P=0.05.

Two males and three females, ages 8-17 years, were followed for 24 to 64months (mean follow-up, 36 months). The presenting diagnoses,radiological findings, overall clinical outcome and complications arelisted in Table 13 below. Comorbidities included behavioral disorders(4/5); respiratory disorders, including sleep apnea (3/5), GERDS (2/5),scoliosis (1/5), tongue-thrusting (1/5). All 5 children had medullarykinking due to an abnormal clivo-axial angle (mean clivo-axial angle,126°). All 5 patients had 1 to 3 mm of ventral brainstem compressionusing the Grabb-Oakes criterion. The associated symptoms and signs arepresented alongside the outcome metrics, before and after surgery asshown in Table 13. Postoperative follow-up was 100%. Preoperative andpostoperative B-pC2 measurements were read independently by aneuroradiologist and are presented in Table 13. Postoperatively, theGrabb-Oakes measurements (Δ) were less than 9 mm, demonstratingreduction of preoperative VBSC.

TABLE 13 Surgical Series Age CAA* Patient (yrs) Primary Diagnosespre/post B-pC2** Outcome Complications F/up (mos #1 9 Episodicrespiratory difficulty, 115°/152° 10 mm +++ ∅ 52 Chiari malformation #213 Encephalomyelopathy, 116°/140° 10 mm +++ ∅ 48 Basilar invagination #317 Encephalomyelopathy, 132°/142° 11 mm +++ ∅ 19 Basilar invagination #413 Myelopathy, Chiari malformation, 129°/139° 11 mm ++ ∅ 17 Scoliosis #515 Severe neck pain, Cranial settling 136°/161°  9 mm +++ ∅ 24 CAA* =Preoperative and postoperative clivo-axial angle; B-pC2** = Grabb-Oakesmeasurement of VBSC, Basion to ventral inferior C2Symptoms

All patients presented with the following symptoms: headache or neckpain, weakness in the upper or lower extremities, sensory changes(hypoesthesias or paresthesias in the upper and lower extremities),clumsiness with frequent falls, uncertain gait, fatigue,gastroesophageal disturbance (reflux or irritable bowel syndrome),respiratory disturbance (including respiratory arrest [pt. #1]), andother respiratory disorders which manifested as sleep apnea, snoring orhistory of frequent awakening. Most reported vestibular, auditory orvisual disturbance and bowel and/or bladder dysfunction. Trophicchanges, including abnormal response of circulation to cold weather orprofuse sweating, occurred in only 1 patient, as shown in Table 13.Every child reported substantial improvement in most symptoms within thefirst postoperative month. This improvement was sustained in everypatient over the duration of follow-up, with one exception. Patient #4,though substantially improved, suffered a recurrence of headaches at 6months postoperatively. This is considered under “complications ofsurgery.” Patient #1 reported total resolution of his respiratoryevents; the other children or their families reported improved sleep andresolution of snoring, frequent awakenings and nightmares.

TABLE 14 Preoperative and postoperative outcomes: clinical findings,metrics SCOSIA stress Brainstem forces Pain disability (N/cm²) (x/100)index ASIA Karnofsky SF-36 Presenting symptoms Postop. symptomaticpreop./ preop./ preop./ preop./ Preop./ Preop./ Patient and signsimprovement postop. postop. postop. postop. Postop. Postop. #1 h/o resp.arrest, Resolution of neck 70/26 70/0 80%/0 M-90/M-100 50%/100% Phys:31/69.1 asthma, sleep apnea, pain and HA, resp. 70/6 P-112/P-112 Mental:22.9/65.2 HA, neck pain, nausea,, abnormalities 70/33 Lt-112/Lt-112anhydrosis Improvement in Decreased gag reflex, strength, coordinationdysdiadochokinesia, No change in Babinski anhydrosis #2 Tonguethrusting, Resolution of tongue 60/13 90/60 55%/5% M-80/M-100 50%/100%Phys: 43/47.6 myoclonic spasms, thrusting, tics, 60/13 P-84/P-112Mental: 37.3/46.8 paresthesias weakness, myoclonic spasms, 46/33Lt-84/P-112 tics, anisocoria, absent strength and sensory gag reflex,hemi- deficit hypoesthesia, Babinski Schizotypal disorder #3Hyperactive, Resolution of 26/6 55/0 55%/0 M-93/M-100 85%/100% Phys:43.5/60.4 sleep apnea, HA, hyperactivity, normal 33/6 P-112/P-112Mental: 47.3/57.2 weakness imbalance, strength, coordination, 60/20Lt-112/Lt-112 incoordination, urinary balance, urinary freq. handflapping urgency and hand Hypoesthesia Hyper- flapping paresthesiasreflexia, Babinski Improved hypopnea reflexes #4 ADHD Resolution ofscoliosis 33/13 70/0 55%/0 M-100/M-100 80%/100% Phys: 37.2/59.5 ChronicHA, emesis, emesis, 40/13 P-75/P-75 Mental: 30.5/58.5 dysphagia Improvedgait, and 26/26 Lt-75/Lt-75 Scoliosis, paresthesia, dysphagia. abnormalgait Recurrence HA at Cat-eye syndrome 6 months. Repeat suboccipcraniectomy #5 Emesis, dysphagia Resolution of HA, back 33/13 35/040%/10% M-100/M-100 80%/100% Phys: 43.7/46 ataxia, freq. falls, pain,sleep walking, 60/13 P-56/P-112 Mental: 53.5/55.4 vertigo, chronic neckemesis, dysphagia and 40/20 Lt-56/Lt-112 and back pain, sleep vertigo.walking, hyperactivity, Normalization of Paresthesias, UE, sensation,strength, fatigue, hyper-reflexia coordination, Asperger's syndromesocialization No fatigueSigns

Preoperative neurological findings included weakness (especially handweakness), poor muscle tone and poor posture, sensory changes,hyper-reflexia and dysdiadochokinesia. One patient was observed to havescoliosis. Sensory changes (hypoesthesia to pinprick) were never painfulor unpleasant, and were frequently ignored or not recognized by thepatient. The gag reflex was decreased or absent in all subjects, thoughusually not associated with dysphagia as shown in Table 13.

Postoperatively, strength, sensation and posture improved in 1 month.Patient #2 improved from mild weakness to normal strength. The scoliosisresolved to normal within the first month in patient #4. Four of the 5patients are performing at academic and athletic levels above theirpreoperative state. Substantial behavioral improvement was reported bythe parents of the 4 subjects with neurobehavioral disorders, butmeasurement of behavior was beyond the scope of this study.

Clinical Metrics

Metrics were obtained from the subjects and their parents by a researchtechnician. Visual analog pain was reduced from a preoperative mean of64 (on a “0 to 100” scale) to a postoperative mean of 12 (t=6.15,P=0.0002 for parametric; V=15, P=0.029 for nonparametric). SF-36physical component summary (PCS) scores improved following surgery(mean, 40-57). These improvements were statistically significant(t=−2.59, P=0.030 for parametric; P=0.031 for nonparametric) andpostoperatively were above the normal mean (sample mean=56.5 versusnormal mean=50±10 SD). Mental component summary (MCS) scores alsoimproved (mean, 38-57), with significance (t=−2.48, P=0.033 forparametric; P=0.031 for nonparametric). Summed ASIA scores increasedfrom a mean of 268.2 to a mean of 309.2, though this increase failed toachieve significance on both parametric and nonparametric tests(t=−1.83, P=0.071 for parametric; P=0.050 for nonparametric). The bulbarsymptom index showed significantly fewer bulbar symptoms followingsurgery (preop. mean=57%, postop. mean=30%; t=6.78, P=0.001 forparametric; V=15, P=0.029 for nonparametric). Karnofsky scoressignificantly improved (mean, 69 preop. to 100 postop, t=−3.97, P=0.008for parametric; P=0.028 for nonparametric).

Stress Modeling

SCOSIA-derived stress values paralleled the patients' clinicalconditions. For instance, high stress values in the motor tracts of thebrainstem and spinal cord signaled weakness. Following surgery, the 68%decrease in calculated stresses within the corticospinal tracts wascongruent with the improved motor performance, as seen in the ASIAscores (P=0.004/0.027). The same was true for sensory symptoms, wherestress decreased by an average of 81% in the dorsal columns(P=0.002/0.028); and for symptoms referable to the respiratory functionand gastrointestinal (GI) function (irritable bowel syndrome [IBS],gastric reflux or GERDS), where stresses in the nucleus solitariusdecreased by 45% (P=0.021/0.05). Resolution of thoracic scoliosis insubject #4 was concordant with decreased stress in the ventral graymatter of the upper thoracic spinal cord (from 60 N/cm² to 5 N/cm²).

With every clinical metric, higher preoperative stress values correlatedwith greater disability (r=0.36 to 0.72), lower Karnofsky values(r=−0.43 to −0.98) and lower physical component summary scores (r=−0.34to −0.60). Correlations between stress values and mental componentsummary scores were more variable (r=0.21 to −0.69). The low sample size(n=5) for these cross-patient comparisons implied that most of thesecorrelations approached, but did not achieve, statistical significance.A very strong correlation between computed stress in the corticospinaltract and Karnofsky score (which achieved significance at r=−0.98,P=0.003) was observed.

The analysis of within-patient changes in SCOSIA estimates of neuraxialstress and patient condition metrics yielded similar results. Patientsexhibiting larger decreases in SCOSIA-derived stress values experiencedproportionate decreases in disability (r=0.36 to 0.52), increases inKarnofsky values (r=−0.08 to −0.99) and increases in PCS (r=−0.22 to−0.35) and MCS scores (r=−0.10 to r=−0.37). The relationship betweenchanges in corticospinal stress and changes in Karnofsky values wasstrong (r=−0.99, P=0.001).

Surgical Complications

There were no neurological deficits resulting from surgery, and no woundproblems. Subject #4 (with a history of craniosynostosis, and cat-eyesyndrome) had undergone a limited suboccipital craniotomy for Chiarimalformation. Six months later, headaches recurred and were suspected torepresent occipital neuralgia. The patient's family refused diagnosticblock of the occipital nerve. The surgeon (F.C.H.) sent the child forevaluation of craniosynostosis; and, later, monitoring of ICP, which wasnormal (<10 cm H₂0). Eighteen months after surgery, the parents soughtenlargement of the suboccipital craniotomy; at 3 years, the headachesappear to have resolved.

Fusion/Stabilization

No subject required blood transfusion. The average duration of surgerywas 3.5 hours. All subjects were discharged within 3 days after surgery.Subjects were placed in hard cervical collars (Miami J™ collars). CTscans at 3 months showed bone fusion in every case. There were nohardware failures. No subjects required revision. Though cervical rangeof movement was decreased, only 1 subject (#1, whose parents had beenoverly protective and insisted that he not move his neck for 6 months)complained of limited neck rotation. The remainder reported nocomplaints of limitation of range of motion at 1 year.

Discussion

The patients in this series were referred for disabling neurologicalsymptoms, which included headaches, bulbar findings and myelopathy. Allsubjects shared abnormality of the clivo-axial angle. The clivo-axialangle to be a surrogate measure of deformative stress in the brainstemand upper spinal cord.

Neuraxial strain is accentuated with flexion of the craniocervicaljunction, as shown in FIGS. 39( a)-39(d). Approximately 22° offlexion/extension occurs at the craniocervical junction. Upon flexion atthe craniocervical junction, there is a lengthening of the brainstem andupper spinal cord, which may reach pathological strains in the contextof an abnormally acute clivo-axial angle, or retroflexed odontoid. Theaddition of “out-of-plane” loading greatly increases the overall VonMises stress. As opposed to the in-line strain that occurs withstretching of the spinal cord upon flexion, “out-of-plane” loading isany deformative stress that occurs horizontally upon the neuraxis, dueto indentation from deformity, stenosis or disc or horizontal strainfrom the dentate ligaments perpendicular to the axis of the neuraxis.Compression from the sides of a viscoelastic cylinder, such as themedulla/upper spinal cord, will create increased longitudinal tensionwithin the neuraxis and perpendicular to the plane of compression. Thusa ventral compression force, like the retroflexed odontoid,“nontraditional” basilar invagination, platybasia and “functionalcranial settling” with hereditary connective tissue disease, results inincreased intra-axial tension. Breig's cadaveric models showed fissuringon the side opposite the compression.

The overall deformative stress generated at the craniocervical junctionmay reach levels where nerve function becomes attenuated; indeed, theaxon is rendered nonconductive and develops pathological changes at astrain ε=0.2.

The present study sought to compute dynamic neuraxial stresses using FEAand images in the flexion, neutral and extension modes. FEA has beenused in the spinal cord to demonstrate that stretch and strain areimportant determinants of pathology in cervical spondylotic myelopathy,and idiopathic anterior motor neuron disease in the cervical cord. Thisis the first study to undertake a mathematical modeling of the brainstemand to compute the stresses before and after surgery. The resultssuggest that the Von Mises stress correlates with neurologicaldysfunction. A decrease in the overall deformative stresses (Von Misesstresses) by the surgical techniques described, in which the clivo-axialangle is normalized, resulted in improvement in neurological functionand pain.

Pathophysiology

This study provides evidence that suggests clinical improvementprimarily relates to alleviation of deformative stress.

Stress Modeling

Maximum stress values from the corticospinal tracts, dorsal columns,nuclei solitarius and dorsal motor nucleus were chosen to compare withclinical findings. The computed stress within each tract decreased aftersurgery. Moreover, stress values and measures of patient condition werealways in the predicted direction—higher stress values were associatedwith higher pain levels and reduced SF-36 (quality of life) scores. Theconcordance of computed neuraxial stresses and clinical metrics supportthe concept that biomechanical stresses generated by stretch and“out-of-plane” loading are important determinants of neurologicaldysfunction.

Although effective, it is recognized that FEA modeling in the neuraxisis nascent and simplistic. The stresses are virtual computations and donot integrate measurements of stress over time and over the full lengthof the tract. The analysis assigns different moduli of elasticity towhite and gray matter but assumes stereotypic response and uniformproperties under various degrees of strain and compression. The moduliof elasticity described for bovine spinal cord was used in thisanalysis. Compression of the bovine cervical spinal cord produced thesame histopathological changes as compression of the human cervicalspinal cord, and there appears to be little difference in the elasticproperties between living and cadaveric spinal cord tissue. The FEAtakes into account neither the strain rate (and it does not account foralteration of compliance due to age, previous injury) nor the metabolicand circulatory factors, such as ischemia.

While other recently described systems generate a single generic modelof the human spinal cord and then simulate flexion, compression andother deformation, SCOSIA parametrically generates a unique model ofboth the medulla oblongata and the spinal cord for each subject, takinginto account the particularities of that patient's anatomy. SCOSIA alsocalculates the shear forces acting at the interface of gray and whitematter tracts.

Irrespective of the aforementioned shortcomings, FEA-generated stresscalculations are helpful in understanding the underlying pathophysiologyof a variety of spinal and brainstem conditions.

Clinical Metrics and Outcomes

Improvements reached statistical significance for all clinical metrics:the VAS, ASIA scale, Karnofsky Index, SF-36: physical component, SF36:mental component and the Bulbar Symptoms Index. The data presented herewas collected by a research assistant. The SF-36 is a widely approvedinstrument for measurement of physical functioning, bodily pain, generalhealth, vitality, social functioning and mental health. It has beenshown to be valid when tested against outcome instruments. While theASIA scale does not measure spasticity, coordination or gait, it isuseful as a metric to detect subtle changes in sensory and motorfunction. The Karnofsky Index was designed as a functional index forcancer patients but has also has been used in other areas as a reliablemeans of assessing function. The Bulbar Symptom Index used in thisreport has not yet been validated but is used by the authors to measureimprovement in the panoply of symptoms generally attributed toneurological dysfunction of the brainstem. A score of 100 representssignificant disability.

The results showed statistically significant improvement of all clinicalmetrics viz., VAS, SF-36, Karnofsky Index, ASIA and Bulbar SymptomIndex, is in agreement with the findings from the work of others.

Comorbidities

There is a large breadth of associated comorbidities in this smallcohort—respiratory disorders and gastroesophageal reflux disease,personality disorders, leg tremors, tongue protrusion (“trombonetongue”) and scoliosis as shown in Table 2. These comorbidities wereresolved or were substantially improved following the craniocervicalsurgery.

Surgical Technique

The need for transoral odontoidectomy in the present surgery wasobviated in many cases by open reduction with manual distraction andextension at the craniocervical junction. A posterior translation of thecranium with respect to the spine and an alignment of the Basion overthe tip of the dens was achieved by manual manipulation during surgery.Patients tolerate the surgery well.

Complications

Postoperatively, a C2 pedicle screw was observed to be adjacent to thevertebral artery in 1 patient (patient #2), in whom the subsequent MRAwas normal. The headaches in patient #4 were thought to be due tooccipital neuralgia. Hence the authors recommend placement of C1 screwsin a manner that avoids encumbrance of the exiting C2 roots.

In one study, a 36% complication rate was reported, but with theexception of 1 patient in whom hyperostosis necessitated a posteriordecompression, these were minor complications. Another researcherreported 2 deaths due to spinal cord injury, sustained when the patientwas turned to the prone position.

A concern in children is the limitation of neck rotation aftercraniospinal fusion. Fifty percent of neck rotation occurs between C1and C2, and approximately 21° of flexion is observed between the occiputand cervical spine. However, only 1 patient of this group complained ofdecreased neck rotation; the remainder reported nearly normal movementat 1 year, presumably as a result of increased rotation of lowercervical levels, compensatory torso rotation and Toyama remodeling ofvertebrae. Delayed complications of occipitocervical fusion in children,when fusion is limited to the upper two cervical vertebrae is unknown.

There is a risk associated with injury to the vertebral artery. Thepublished data for craniospinal fusion stabilization shows that themorbidity of this operation compares favorably with other common spinalsurgeries, such as lumbar discectomy.

Conclusion

Conventional radiographic assessment of basilar invagination does notreveal the more subtle forms of ventral brainstem compression anddeformation. Open reduction of craniospinal deformity (normalization ofclivo-axial angle), stabilization and surgical fusion were effective inimproving pain and neurological function in subjects withcervicomedullary disorders resulting from deformative stress.

FEA was used to compute neuraxial deformative stress in the context ofcervicomedullary disorders due to Chiari malformation and basilarinvagination. Surgical correction of the deformity resulted inimprovement of computed Von Mises stress in selected anatomicalstructures, which was concordant with relief of pain and neurologicaldeficits. FEA may offer new insight into the effect of pressure andstrain on the neuraxis at the cervicomedullary junction.

Prophetic Example 5

In a prophetic study for treating a neurological disorder, a patientwith an existing neurological disorder is first examined to determinethe extent of the patient's neuraxial stress, specifically whether thepatient has abnormal deformative neuraxial stress. As part of thisdetermination, aspects of one or more aspects of a patient's anatomicalfeatures, such as the occipitocervical junction, brainstem and/or spinalcord, preferably one or more physiological features forming theneuraxial angle, clivo-axial angle and/or basal angle, are measuredand/or calculated from radiographic images of the patient'soccipitocervical junction, brainstem and/or spinal cord. Exemplaryanatomical features include the length of an outside perimeter, insiderperimeter or midline of the brainstem and spinal cord; the width orthickness of multiple regions of the brainstem and spinal cord; and thelength of medulla and upper spinal cord on the ventral and dorsalsurface (for the fourth ventral). These measurements and/or calculationsmay be performed using a medical imaging computational device thatsupports, runs and/or is controlled by a computer readable software foridentifying, calculating and/or measuring the neuraxial angle,clivo-axial angle, basal angle or combinations thereof. This informationmay then be used to calculate the neuraxial stress. Preferably, themedical imaging computational device and/or computer readable softwaremay be used to calculate the neuraxial stress from the measured and/orcalculated aspects.

Alternatively, a computer generated model of the brainstem and spinalcord that incorporates patient-specific anatomical data, such asdeformity over the odontoid process, lengthening of brainstem and spinalcord with flexion and compression of the spinal cord by a herniated discor spur, may be developed to parametrically generate specific FEA modelsfor each patient. The computations derived from these models undergoingflexion and extension can be used to generate estimates of the stressesexisting within the brainstem and spinal cord in the neutral, flexionand extension conditions, specifically the neuraxial stress.

Based on the neuraxial stress, the method further involves determiningwhether the patient's neuraxial stress is contributing to or causativeof the neurological disorder. This may be accomplished by determiningwhether the neuraxial stress, particularly the change in stress duringfull flexion and extension, is within an abnormal range. The neuraxialstress alone may be determinative of a correlation with the neurologicaldisorder. Alternatively, the following additional factors may also beevaluated: (2) the presence of neck pain and/or headache; (3) thepresence of two or more bulbar findings set forth in Table 2; (4) thepresence of myelopathy; (5) a finding of cranio-vertebral instability;and (6) the presence of an abnormal neuraxial and/or abnormalclivo-axial angle. When two or more of the aforementioned factors arepresent, the abnormal deformative neuraxial stress either contributes toand/or causes the patient's neurological symptoms and/or neurologicaldisorder.

Subsequently, the neurological disorder may be treated by correcting theneuraxial stress to normal stress ranges. This may be accomplished bysurgically adjusting and stabilizing the patient's craniospinal junctionin a manner that normalizes the stresses of the CNS. The neuraxialdeformation may be corrected using any conventional spinal stabilizationsystem. Preferably, the abnormal neuraxial stress is corrected using oneof the spinal stabilization devices shown in FIGS. 1-34 and thecorresponding method for implanting the spinal stabilization device ofthe present invention. Specifically, the neuraxial deformation may bereduced by surgically normalizing the clivo-axial angle, neuraxial angleand/or basal angle to within acceptable limits, thereby normalizing theneuraxial stress to acceptable and treating the neurological disorder.

Prophetic Example 6

In a prophetic example, the same method described in prophetic example 5is performed. In this example, the patient is diagnosed with and themethod is used to treat at least one behavioral neurological disorderselected from psychological disorders, such as anxiety, bipolardisorder, scizophrenia, and depression; autism spectrum disorders, suchas autism and Asperger syndrome; and attention deficit hyperactivitydisorder.

Prophetic Example 7

In a prophetic example, the same method described in prophetic example 5is performed. In this example, the patient is diagnosed with and themethod is used to treat a hypermobility connective tissue disorder, suchas Ehlers Danlos Syndrome.

Prophetic Example 8

In a prophetic study for treating cranio-vertebral instability, themethod involves accessing the presence of cranio-vertebral instabilityin a patient using the factors set forth in the cranio-vertebralinstability definition. Determining the existence of an abnormalclivo-axial angle and/or an abnormal neuraxial angle as part of thisassessment. The patient may then be treated by decompressing any areasof the neuraxis that are compressed or deformed as a result of out ofplane loading. Subsequently, the method may involve correcting theneuraxial angle and/or clivo-axial angle so that it is normalized withacceptable limits. This may be accomplished by surgically adjusting andstabilizing the patient's craniospinal junction in a manner thatnormalizes the neuraxial angle and/or clivo-axial angle. The abnormalneuraxial angle and/or abnormal clivo-axial angle may be corrected usinga conventional spinal stabilization system. Preferably, however,neuraxial angle and/or clivo-axial angle is corrected using one of thespinal stabilization devices shown in FIGS. 1-34 and the correspondingmethod for implanting the spinal stabilization device described in thepresent invention. Specifically, a neuraxial deformation may be reducedby surgically normalizing the clivo-axial angle and/or neuraxial angleto within acceptable limits, thereby normalizing the neuraxial stress toacceptable and treating the cranio-vertebral instability disorder.

Prophetic Example 9

The method for treating a neurological disorder arising fromcranio-vertebral instability by treating the underlying cranio-vertebralinstability in the same manner as described in Example 8.

Prophetic Example 10

In a prophetic study for treating a neurological disorder, a patientdiagnosed with a neurological disorder is examined to access thepresence of a neuraxial deformity. Specifically, the patient is examinedto measure and/or calculate the clivo-axial angle and/or neuraxialangle, so as to determine whether the patient has an abnormalclivo-axial angle and/or neuraxial angle. As part of this determination,one or more aspects of a patient's anatomical features, specifically theoccipitocervical junction, brainstem and/or spinal cord, preferably thephysiological features forming the neuraxial angle and/or clivo-axialangle, are measured and/or calculated from radiographic images of thepatient's occipitocervical junction, brainstem and/or spinal cord.Exemplary anatomical features include the length of an outsideperimeter, insider perimeter or midline of the brainstem and spinalcord; the width or thickness of multiple regions of the brainstem andspinal cord; and the length of medulla and upper spinal cord on theventral and dorsal surface (for the fourth ventral). These measurementsand/or calculations may be performed using a medical imagingcomputational device that supports, runs and/or is controlled by acomputer readable software for identifying, calculating and/or measuringthe neuraxial angle and/or clivo-axial angle or combinations thereof.

Based on this information, the method further involves determiningwhether the neuraxial deformity, specifically the patient's abnormalneuraxial angle and/or abnormal clivo-axial angle is contributing to orcausative of the neurological disorder. This may be accomplished byusing the medical imaging computational device and software program tocalculate neuraxial stress and/or strain resulting from the neuroaxialdeformity and determining whether it is correlated to the neurologicaldisorder, in the same manner as in Example 5.

Subsequently, the neurological disorder may be treated by correcting theneuraxial angle and/or clivo-axial angle so that it is normalized withacceptable limits. This may be accomplished by surgically adjusting andstabilizing the patient's craniospinal junction in a manner thatnormalizes the neuraxial angle and/or clivo-axial angle. The abnormalneuraxial angle and/or abnormal clivo-axial angle may be corrected usinga conventional spinal stabilization system. Preferably, however,neuraxial angle and/or clivo-axial angle is corrected using one of thespinal stabilization devices shown in FIGS. 1-34 and the correspondingmethod for implanting the spinal stabilization device described in thepresent invention. Specifically, the neuraxial deformation may bereduced by surgically normalizing the clivo-axial angle, neuraxial angleand/or basal angle to within acceptable limits, thereby normalizing theneuraxial stress to acceptable and treating the neurological disorder.

Prophetic Example 11

In a prophetic example, the same method described in prophetic example10 is performed. In this example, the patient is diagnosed with and themethod is used to treat at least one behavioral neurological disorderselected from psychological disorders, such as anxiety, bipolardisorder, scizophrenia, and depression; autism spectrum disorders, suchas autism and Asperger syndrome; and attention deficit hyperactivitydisorder.

Prophetic Example 12

In a prophetic example, the same method described in prophetic example10 is performed. In this example, the patient is diagnosed with and themethod is used to treat a hypermobility connective tissue disorder, suchas Ehlers Danlos Syndrome

The foregoing examples have been presented for the purpose ofillustration and description and are not to be construed as limiting thescope of the invention in any way. The scope of the invention is to bedetermined from the claims appended hereto.

What is claimed is:
 1. A method for treating a neurological disordercomprising the steps of: calculating a neuraxial stress of anindividual; determining that an abnormal neuraxial stress exists;determining whether the neurological disorder is attributed at least inpart to the calculated neuraxial stress; and treating the neurologicaldisorder by normalizing the neuraxial stress.
 2. The method of claim 1,further comprising the step of measuring of one or more anatomicalaspects of the occipitocervical junction selected from the groupconsisting of: neuraxial angle, clivo-axial angle, basal angle, medullalength, upper spinal cord length and combinations thereof, wherein theneuraxial stress is calculated based on the measured one or moreanatomical components of the occipitocervical junction.
 3. The method ofclaim 1, further comprising the step of creating a computer generatedmodel of a brainstem and a spinal cord of the individual and wherein theneuraxial stress is calculated using finite element analysis of thecomputer generated model.
 4. The method of claim 3, wherein the step ofcalculating the neuraxial stress comprises calculating the neuraxialstress of the brainstem and the spinal cord in one or more conditionsselected from the group consisting of: a neutral condition, flexion,extension, compression and combinations thereof.
 5. The method of claim1, further comprising the step of calculating the neuraxial stress underload, and comparing the calculated neuraxial stress to a restingneuraxial stress to determine whether the neurological disorder isattributed at least in part to the neuraxial stress.
 6. The method ofclaim 5, wherein the step of determining whether the neurologicaldisorder is attributed at least in part to the neuraxial stress furthercomprises evaluating the presence of neck pain and/or headache; thepresence of bulbar findings; the presence of myelopathy; the presence ofcraniovertebral instability; and the presence of an abnormal neuraxialangle or abnormal clivo-axial angle.
 7. The method of claim 1, whereinthe step of treating the neurological disorder comprises attaching aplate to a cranium of the individual and connecting a rod member to theplate and a vertebra of the individual so as to stabilize a craniospinaljunction of the individual and normalize the neuraxial stress.
 8. Themethod of claim 7, wherein the neuraxial stress is normalized bycorrecting a clivo-axial angle of the individual to about 150° to about170°.
 9. The method of claim 1, wherein the neurological disorder is aneurological behavioral disorder.
 10. The method of claim 1, wherein theneurological disorder is autism spectrum disorder.
 11. The method ofclaim 1, wherein the neurological disorder is hypermobility connectivetissue disorder.
 12. The method of claim 1, wherein the neurologicaldisorder is Ehlers-Danlos syndrome.
 13. A method for treating aneurological behavioral disorder comprising the steps of: determiningwhether a neuraxial deformity causing a neuraxial stress exists in anindividual diagnosed with a neurological behavioral disorder;determining that the neuraxial deformity is substantially contributingto or causes the neurological behavioral disorder; and treating theneurological behavioral disorder by normalizing a clivo-axial angle. 14.The method of claim 13, wherein the neuraxial deformity is an abnormalclivo-axial angle and wherein whether a neuraxial deformity anindividual diagnosed with a neurological behavioral disorder issubstantially contributing to or causes the neurological behavioraldisorder is determined from the neuraxial stress of the individual. 15.The method of claim 14, wherein the step of determining whether theneurological behavioral disorder is attributed at least in part to theneuraxial stress further comprises evaluating the presence of neck painand/or headache; the presence of bulbar findings; the presence ofmyelopathy; the presence of craniovertebral instability; and thepresence of an abnormal neuraxial angle or abnormal clivo-axial angle.16. The method of claim 13, wherein the step of treating theneurological behavioral disorder comprises attaching a plate to acranium of the individual and connecting a rod member to the plate and avertebra of the individual so as to normalize the clivo-axial angle. 17.A method for treating cranio-vertebral instability comprising the stepsof: treating an individual having an existing cranio-vertebralinstability by accessing the presence of an abnormal neuraxial angleand/or abnormal clivo-axial angle in the individual; and normalizing theclivo-axial angle or the neuraxial angle.
 18. The method of claim 17,wherein the step of normalizing the clivo-axial angle or the neuraxialangle comprises attaching a plate to a cranium of the individual andconnecting a rod member to the plate and to a vertebra of the individualso as to normalize the clivo-axial angle or the neuraxial angle.
 19. Amethod for treating a neurological disorder resulting fromcranio-vertebral instability comprising the steps of: determining thepresence a pathological deformative stress from measuring a neuraxialangle and/or abnormal clivo-axial angle in an individual; and treatingthe neurological disorder resulting from cranio-vertebral instability bynormalizing a clivo-axial angle or a neuraxial angle of the individual.20. The method of claim 19, wherein the step of normalizing theclivo-axial angle or the neuraxial angle comprises attaching a plate toa cranium of the individual and connecting a rod member to the plate andto a vertebra of the individual so as to normalize the clivo-axial angleor the neuraxial angle.